Pathophysiology of Overactive Bladder and Pharmacologic Treatments Including β3-Adrenoceptor Agonists -Basic Research Perspectives
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Overactive bladder (OAB) is a symptom-based syndrome defined by urinary urgency, frequency, and nocturia with or without urge incontinence. The causative pathology is diverse; including bladder outlet obstruction (BOO), bladder ischemia, aging, metabolic syndrome, psychological stress, affective disorder, urinary microbiome, localized and systemic inflammatory responses, etc. Several hypotheses have been suggested as mechanisms of OAB generation; among them, neurogenic, myogenic, and urothelial mechanisms are well-known hypotheses. Also, a series of local signals called autonomous myogenic contraction, micromotion, or afferent noises, which can occur during bladder filling, may be induced by the leak of acetylcholine (ACh) or urothelial release of adenosine triphosphate (ATP). They can be transmitted to the central nervous system through afferent fibers to trigger coordinated urgency-related detrusor contractions. Antimuscarinics, commonly known to induce smooth muscle relaxation by competitive blockage of muscarinic receptors in the parasympathetic postganglionic nerve, have a minimal effect on detrusor contraction within therapeutic doses. In fact, they have a predominant role in preventing signals in the afferent nerve transmission process. β3-adrenergic receptor (AR) agonists inhibit afferent signals by predominant inhibition of mechanosensitive Aδ-fibers in the normal bladder. However, in pathologic conditions such as spinal cord injury, it seems to inhibit capsaicin-sensitive C-fibers. Particularly, mirabegron, a β3-agonist, prevents ACh release in the BOO-induced detrusor overactivity model by parasympathetic prejunctional mechanisms. A recent study also revealed that vibegron may have 2 mechanisms of action: inhibition of ACh from cholinergic efferent nerves in the detrusor and afferent inhibition via urothelial β3-AR.
Abstract
Overactive bladder (OAB) is a symptom-based syndrome defined by urinary urgency, frequency, and nocturia with or without urge incontinence. The causative pathology is diverse; including bladder outlet obstruction (BOO), bladder ischemia, aging, metabolic syndrome, psychological stress, affective disorder, urinary microbiome, localized and systemic inflammatory responses, etc. Several hypotheses have been suggested as mechanisms of OAB generation; among them, neurogenic, myogenic, and urothelial mechanisms are well-known hypotheses. Also, a series of local signals called autonomous myogenic contraction, micromotion, or afferent noises, which can occur during bladder filling, may be induced by the leak of acetylcholine (ACh) or urothelial release of adenosine triphosphate (ATP). They can be transmitted to the central nervous system through afferent fibers to trigger coordinated urgency-related detrusor contractions. Antimuscarinics, commonly known to induce smooth muscle relaxation by competitive blockage of muscarinic receptors in the parasympathetic postganglionic nerve, have a minimal effect on detrusor contraction within therapeutic doses. In fact, they have a predominant role in preventing signals in the afferent nerve transmission process. β3-adrenergic receptor (AR) agonists inhibit afferent signals by predominant inhibition of mechanosensitive Aδ-fibers in the normal bladder. However, in pathologic conditions such as spinal cord injury, it seems to inhibit capsaicin-sensitive C-fibers. Particularly, mirabegron, a β3-agonist, prevents ACh release in the BOO-induced detrusor overactivity model by parasympathetic prejunctional mechanisms. A recent study also revealed that vibegron may have 2 mechanisms of action: inhibition of ACh from cholinergic efferent nerves in the detrusor and afferent inhibition via urothelial β3-AR.
참고문헌 (225)
- Irwin DE, "Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries : results of the EPIC study", Eur Urol, 50, pp.1306~1314 (2006)
- Stewart WF, "Prevalence and burden of overactive bladder in the United States", World J Urol, 20, pp.327~336 (2003)
- Milsom I, "How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study", BJU Int, 87, pp.760~766 (2001)
- Abrams P, "Standardisation Sub-committee of the International Continence Society. The standardisation of terminology of lower urinary tract function : report from the Standardisation Sub-committee of the International Continence Society", Neurourol Urodyn, 21, pp.167~178 (2002)
- Moon S, "The relationship between nocturia and mortality : data from the National Health and Nutrition Examination Survey", Int Neurourol J, 26, pp.144~152 (2022)
- Moon S, "Association of nocturia and cardiovascular disease : data from the National Health and Nutrition Examination Survey", Neurourol Urodyn, 40, pp.1569~1575 (2021)
- Hashim H, "Is the bladder a reliable witness for predicting detrusor overactivity?", J Urol, 175, pp.191~194 (2006)
- Shen JD, "Review of animal models to study urinary bladder function", Biology(Basel), 10, pp.1316~ (2021)
- Kwon J, "Continuous administration of mirabegron has advantages in inhibition of central sensitization compared with short-term treatment cessation in a mouse model of overactive bladder", Neurourol Urodyn, 41, pp.1355~1363 (2022)
- de Groat WC, "A neurologic basis for the overactive bladder", Urology, 50, pp.36~52 (1997)
- Turner WH, "Smooth muscle of the bladder in the normal and the diseased state : pathophysiology, diagnosis and treatment", Pharmacol Ther, 75, pp.77~110 (1997)
- Birder LA, "Urothelial mucosal signaling and the overactive bladder-ICI-RS 2013", Neurourol Urodyn, 33, pp.597~601 (2014)
- Andersson KE, "Antimuscarinics for treatment of overactive bladder", Lancet Neurol, 3, pp.46~53 (2004)
- Gillespie JI, "The autonomous bladder : a view of the origin of bladder overactivity and sensory urge", BJU Int, 93, pp.478~483 (2004)
- Holstege G, "Anatomical and physiological observations on supraspinal control of bladder and urethral sphincter muscles in the cat", J Comp Neurol, 250, pp.449~461 (1986)
- Griffiths D, "Brain control of normal and overactive bladder", J Urol, 174, pp.1862~1867 (2005)
- Andersson KE, "CNS involvement in overactive bladder : pathophysiology and opportunities for pharmacological intervention", Drugs, 63, pp.2595~2611 (2003)
- Andersson KE, "Antimuscarinic mechanisms and the overactive detrusor : an update", Eur Urol, 59, pp.377~386 (2011)
- Fowler CJ, "The neural control of micturition", Nat Rev Neurosci, 9, pp.453~466 (2008)
- Yokoyama O, "Influence of anesthesia on bladder hyperactivity induced by middle cerebral artery occlusion in the rat", Am J Physiol, 273, pp.R1900~R1907 (1997)
- Albanese A, "Bladder hyperreflexia induced in marmosets by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine", Neurosci Lett, 87, pp.46~50 (1988)
- Yoshimura N, "The dopamine D1 receptor agonist SKF 38393 suppresses detrusor hyperreflexia in the monkey with parkinsonism induced by 1-methyl4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP)", Neuropharmacology, 32, pp.315~321 (1993)
- Griffiths D, "Bladder control, urgency, and urge incontinence : evidence from functional brain imaging", Neurourol Urodyn, 27, pp.466~474 (2008)
- Tadic SD, "Brain activity underlying impaired continence control in older women with overactive bladder", Neurourol Urodyn, 31, pp.652~658 (2012)
- Kessler TM, "Effect of thalamic deep brain stimulation on lower urinary tract function", Eur Urol, 53, pp.607~612 (2008)
- Yoshimura N, "Lower urinary tract symptoms(LUTS)and bladder afferent activity", Neurourol Urodyn, 26(6 Suppl), pp.908~913 (2007)
- O’Reilly BA, "P2X receptors and their role in female idiopathic detrusor instability", J Urol, 167, pp.157~164 (2002)
- De Laet K, "Systemic oxybutynin decreases afferent activity of the pelvic nerve of the rat : new insights into the working mechanism of antimuscarinics", Neurourol Urodyn, 25, pp.156~161 (2006)
- Aizawa N, "Effects of CL316, 243, a beta 3-adrenoceptor agonist, and intravesical prostaglandin E2on the primary bladder afferent activity of the rat", Neurourol Urodyn, 29, pp.771~776 (2010)
- de Groat WC, "Mechanisms underlying the recovery of urinary bladder function following spinal cord injury", J Auton Nerv Syst, 30(Suppl), pp.S71~S77 (1990)
- de Groat WC, "Organization of the sacral parasympathetic reflex pathways to the urinary bladder and large intestine", J Auton Nerv Syst, 3, pp.135~160 (1981)
- Häbler HJ, "Activation of unmyelinated afferent fibres by mechanical stimuli and inflammation of the urinary bladder in the cat", J Physiol, 425, pp.545~562 (1990)
- De Groat WC, "Nervous control of the urinary bladder of the cat", Brain Res, 87, pp.201~211 (1975)
- Mallory B, "Electrophysiological study of micturition reflexes in rats", Am J Physiol, 257, pp.R410~R421 (1989)
- Maggi CA, "Maggi CA: The Autonomic Nervous System, Vol. 3, Nervous Control ofthe Urogenital System", pp.383~422 (1993), Harwood Academic Publishers
- Geirsson G, "Clinical and urodynamic effects of intravesical capsaicin treatment in patients with chronic traumatic spinal detrusor hyperreflexia", J Urol, 154, pp.1825~1829 (1995)
- Das A, "Intravesical capsaicin in neurologic impaired patients with detrusor hyperreflexia", J Spinal Cord Med, 19, pp.190~193 (1996)
- Somogyi GT, "Frequency dependence of muscarinic facilitation of transmitter release in urinary bladder strips from neurally intact or chronic spinal cord transected rats", Br J Pharmacol, 125, pp.241~246 (1998)
- Brading AF, "A myogenic basis for the overactive bladder", Urology, 50(6A Suppl), pp.57~67 (1997)
- Brading AF, "Ischemia as an etiological factor in bladder instability : implications for therapy", Adv Exp Med Biol, 539, pp.255~269 (2003)
- Sibley GN, "Developments in our understanding of detrusor instability", Br J Urol, 80(Suppl 1), pp.54~61 (1997)
- Drake MJ, "Model of peripheral autonomous modules and a myovesical plexus in normal and overactive bladder function", Lancet, 358, pp.401~403 (2001)
- Sui G, "Aberrant Ca2+ oscillations in smooth muscle cells from overactive human bladders", Cell Calcium, 45, pp.456~464 (2009)
- German K, "Physiological and morphometric studies into the pathophysiology of detrusor hyperreflexia in neuropathic patients", J Urol, 153, pp.1678~1683 (1995)
- Mills IW, "Studies of the pathophysiology of idiopathic detrusor instability : the physiological properties of the detrusor smooth muscle and its pattern of innervation", J Urol, 163, pp.646~651 (2000)
- Birder L, "Urothelial signaling", Physiol Rev, 93, pp.653~680 (2013)
- Ikeda Y, "Urotheliogenic modulation of intrinsic activity in spinal cord-transected rat bladders : role of mucosal muscarinic receptors", Am J Physiol Renal Physiol, 295, pp.F454~F461 (2008)
- Andersson KE, "Bladder activation : afferent mechanisms", Urology, 59(5 Suppl 1), pp.43~50 (2002)
- Birder LA, "Mechanisms of disease : involvement of the urothelium in bladder dysfunction", Nat Clin Pract Urol, 4, pp.46~54 (2007)
- Freeman RS, "NGF deprivation-induced gene expression : after ten years, where do we stand?", Prog Brain Res, 146, pp.111~126 (2004)
- Frias B, "Transient receptor potential vanilloid 1 mediates nerve growth factor-induced bladder hyperactivity and noxious input", BJU Int, 110, pp.E422~E428 (2012)
- Hashimoto M, "Sex differences in lower urinary tract function in mice with or without spinal cord injury", Neurourol Urodyn, 43, pp.267~275 (2024)
- Fovaeus M, "A non-nitrergic smooth muscle relaxant factor released from rat urinary bladder by muscarinic receptor stimulation", J Urol, 161, pp.649~653 (1999)
- Hawthorn MH, "Urothelium-derived inhibitory factor(s)influences on detrusor muscle contractility in vitro", Br J Pharmacol, 129, pp.416~419 (2000)
- Gillespie JI, "On the origins of the sensory output from the bladder : the concept of afferent noise", BJU Int, 103, pp.1324~1333 (2009)
- Drake MJ, "The potential role of unregulated autonomous bladder micromotions in urinary storage and voiding dysfunction; overactive bladder and detrusor underactivity", BJU Int, 119, pp.22~29 (2017)
- Drake MJ, "Partial outlet obstruction enhances modular autonomous activity in the isolated rat bladder", J Urol, 170, pp.276~279 (2003)
- Van Os-Bossagh P, "Micromotions of bladder wall in chronic pelvic pain(CPP) : a pilot study", Int Urogynecol J Pelvic Floor Dysfunct, 12, pp.89~96 (2001)
- Abrams PH, "The results of prostatectomy : a symptomatic and urodynamic analysis of 152 patients", J Urol, 121, pp.640~642 (1979)
- Housami F, "Persistent detrusor overactivity after transurethral resection of the prostate", Curr Urol Rep, 9, pp.284~290 (2008)
- Price DA, "The unstable bladder and prostatectomy", Br J Urol, 52, pp.529~531 (1980)
- Fusco F, "Progressive bladder remodeling due to bladder outlet obstruction : a systematic review of morphological and molecular evidences in humans", BMC Urol, 18, pp.15~ (2018)
- Jiang YH, "Urothelial dysfunction, suburothelial inflammation and altered sensory protein expression in men with bladder outlet obstruction and various bladder dysfunctions : correlation with urodynamics", J Urol, 196, pp.831~837 (2016)
- Cheng F, "A constrained mixture-micturition-growth(CMMG)model of the urinary bladder : application to partial bladder outlet obstruction(BOO)", J Mech Behav Biomed Mater, 134, pp.105337~ (2022)
- Niemczyk G, "Expression of toll-like receptors in the animal model of bladder outlet obstruction", Biomed Res Int, 2020, pp.6632359~ (2020)
- Kai W, "Urethral meatus stricture BOO stimulates bladder smooth muscle cell proliferation and pyroptosis via IL 1β and the SGK1 NFAT2 signaling pathway", Mol Med Rep, 22, pp.219~226 (2020)
- Hughes FM Jr, "The NLRP3 inflammasome mediates inflammation produced by bladder outlet obstruction", J Urol, 195, pp.1598~1605 (2016)
- Hughes FM Jr, "Bladder decompensation and reduction in nerve density in a rat model of chronic bladder outlet obstruction are attenuated with the NLRP3 inhibitor glyburide", Am J Physiol Renal Physiol, 316, pp.F113~F120 (2019)
- Steers WD, "Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function", J Clin Invest, 88, pp.1709~1715 (1991)
- Birder LA, "Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1", Nat Neurosci, 5, pp.856~860 (2002)
- Kim JC, "Nerve growth factor and vanilloid receptor expression, and detrusor instability, after relieving bladder outlet obstruction in rats", BJU Int, 94, pp.915~918 (2004)
- Reynolds WS, "Does central sensitization help explain idiopathic overactive bladder?", Nat Rev Urol, 13, pp.481~491 (2016)
- Baker SA, "Role of TREK-1 potassium channel in bladder overactivity after partial bladder outlet obstruction in mouse", J Urol, 183, pp.793~800 (2010)
- Baker SA, "Methionine and its derivatives increase bladder excitability by inhibiting stretch-dependent K(+)channels", Br J Pharmacol, 153, pp.1259~1271 (2008)
- Salkoff L, "High-conductance potassium channels of the SLO family", Nat Rev Neurosci, 7, pp.921~931 (2006)
- Herrera GM, "Urinary bladder instability induced by selective suppression of the murine small conductance calcium-activated potassium(SK3)channel", J Physiol, 551, pp.893~903 (2003)
- Meredith AL, "Overactive bladder and incontinence in the absence of the BK large conductance Ca2+-activated K+ channel", J Biol Chem, 279, pp.36746~36752 (2004)
- Petkov GV, "Beta1-subunit of the Ca2+-activated K+ channel regulates contractile activity of mouse urinary bladder smooth muscle", J Physiol, 537, pp.443~452 (2001)
- Kita M, "Effects of bladder outlet obstruction on properties of Ca2+-activated K+ channels in rat bladder", Am J Physiol Regul Integr Comp Physiol, 298, pp.R1310~R1319 (2010)
- Kim JC, "Muscarinic and purinergic receptor expression in the urothelium of rats with detrusor overactivity induced by bladder outlet obstruction", BJU Int, 101, pp.371~375 (2008)
- Andersson KE, "Antimuscarinics and the overactive detrusor--which is the main mechanism of action?", Eur Urol, 43, pp.1~5 (2003)
- de Groat WC, "The urothelium in overactive bladder : passive bystander or active participant?", Urology, 64(6 Suppl 1), pp.7~11 (2004)
- Cook SP, "ATP, pain and a full bladder", Nature, 407, pp.951~952 (2000)
- Zhong Y, "Bladder and cutaneous sensory neurons of the rat express different functional P2X receptors", Neuroscience, 120, pp.667~675 (2003)
- Komninos C, "Obstruction-induced alterations within the urinary bladder and their role in the pathophysiology of lower urinary tract symptomatology", Can Urol Assoc J, 8, pp.E524~E530 (2014)
- Hsiao SM, "Comparison of vascularization and overall perfusion of the bladder wall between women with and without overactive bladder syndrome", Sci Rep, 10, pp.7549~ (2020)
- Zhao Z, "Progressive changes in detrusor function and micturition patterns with chronic bladder ischemia", Investig Clin Urol, 57, pp.249~259 (2016)
- Yang JH, "Regulation of cellular stress signaling in bladder ischemia", Res Rep Urol, 12, pp.391~402 (2020)
- Azadzoi KM, "Molecular reactions and ultrastructural damage in the chronically ischemic bladder", J Urol, 186, pp.2115~2122 (2011)
- Ford ES, "Prevalence of the metabolic syndrome among US adults : findings from the third National Health and Nutrition Examination Survey", JAMA, 287, pp.356~359 (2002)
- Alberti KG, "IDF Epidemiology Task Force Consensus Group. The metabolic syndrome--a new worldwide definition", Lancet, 366, pp.1059~1062 (2005)
- Bunn F, "Is there a link between overactive bladder and the metabolic syndrome in women? A systematic review of observational studies", Int J Clin Pract, 69, pp.199~217 (2015)
- He Q, "Metabolic syndrome, inflammation and lower urinary tract symptoms : possible translational links", Prostate Cancer Prostatic Dis, 19, pp.7~13 (2016)
- Rohrmann S, "Third National Health and Nutrition Examination Survey. Association between serum concentrations of micronutrients and lower urinary tract symptoms in older men in the Third National Health and Nutrition Examination Survey", Urology, 64, pp.504~509 (2004)
- Lee WC, "The impact of diabetes on the lower urinary tract dysfunction", JTUA, 20, pp.155~161 (2009)
- Liu RT, "Prevalence of overactive bladder and associated risk factors in 1359 patients with type 2 diabetes", Urology, 78, pp.1040~1045 (2011)
- Steers WD, "An enlarged prostate is diagnosed more often in patients with type 2 diabetes", Rev Urol, 4, pp.S7~S18 (2002)
- Tong YC, "Alterations of M(2)-muscarinic receptor protein and mRNA expression in the urothelium and muscle layer of the streptozotocin-induced diabetic rat urinary bladder", Neurosci Lett, 406, pp.216~221 (2006)
- Cheng JT, "Changes of M3-muscarinic receptor protein and mRNA expressions in the bladder urothelium and muscle layer of streptozotocin-induced diabetic rats", Neurosci Lett, 423, pp.1~5 (2007)
- Nirmal J, "Functional and molecular characterization of hyposensitive underactive bladder tissue and urine in streptozotocin-induced diabetic rat", PLoS One, 9, pp.e102644~ (2014)
- Tong YC, "Alterations of M2, 3-muscarinic receptor protein and mRNA expression in the bladder of the fructose fed obese rat", J Urol, 178, pp.1537~1542 (2007)
- Lee WC, "Pathophysiological studies of overactive bladder and bladder motor dysfunction in a rat model of metabolic syndrome", J Urol, 186, pp.318~325 (2011)
- Kershen RT, "Blood flow, pressure and compliance in the male human bladder", J Urol, 168, pp.121~125 (2002)
- Azadzoi KM, "Oxidative modification of mitochondrial integrity and nerve fiber density in the ischemic overactive bladder", J Urol, 183, pp.362~369 (2010)
- Di Meo S, "Mitochondria in exercise-induced oxidative stress", Biol Signals Recept, 10, pp.125~140 (2001)
- Yu HJ, "Overactive bladder syndrome among community-dwelling adults in Taiwan : prevalence, correlates, perception, and treatment seeking", Urol Int, 77, pp.327~333 (2006)
- Nobe K, "Alterations of glucose-dependent and-independent bladder smooth muscle contraction in spontaneously hypertensive and hyperlipidemic rat", J Pharmacol Exp Ther, 324, pp.631~642 (2008)
- Yoshida M, "The effects of chronic hyperlipidemia on bladder function in myocardial infarction-prone Watanabe heritable hyperlipidemic(WHHLMI)rabbits", Neurourol Urodyn, 29, pp.1350~1354 (2010)
- Azadzoi KM, "Increased leukotriene and prostaglandin release, and overactivity in the chronically ischemic bladder", J Urol, 169, pp.1885~1891 (2003)
- Lawrence JM, "Pelvic floor disorders, diabetes, and obesity in women : findings from the Kaiser Permanente Continence Associated Risk Epidemiology Study", Diabetes Care, 30, pp.2536~2541 (2007)
- Yang SS, "Alpha1-Adrenergic blockers in young men with primary bladder neck obstruction", J Urol, 168, pp.571~574 (2002)
- Chess-Williams R, "Chronic psychological stress and lower urinary tract symptoms", Low Urin Tract Symptoms, 13, pp.414~424 (2021)
- Vrijens D, "Affective symptoms and the overactive bladder-a systematic review", J Psychosom Res, 78, pp.95~108 (2015)
- Mills KA, "Psychological stress induced bladder overactivity in female mice is associated with enhanced afferent nerve activity", Sci Rep, 11, pp.17508~ (2021)
- West EG, "Bladder overactivity induced by psychological stress in female mice is associated with enhanced bladder contractility", Life Sci, 265, pp.118735~ (2021)
- Johnson JD, "Catecholamines mediate stress-induced increases in peripheral and central inflammatory cytokines", Neuroscience, 135, pp.1295~1307 (2005)
- Klausner AP, "Corticotropin releasing factor : a mediator of emotional influences on bladder function", J Urol, 172, pp.2570~2573 (2004)
- Pacák K, "Stressor-specific activation of the hypothalamic-pituitary-adrenocortical axis", Physiol Res, 49(Suppl 1), pp.S11~S17 (2000)
- Ulrich-Lai YM, "Neural regulation of endocrine and autonomic stress responses", Nat Rev Neurosci, 10, pp.397~409 (2009)
- Ullmann E, "Offensive behavior, striatal glutamate metabolites, and limbic-hypothalamic-pituitary-adrenal responses to stress in chronic anxiety", Int J Mol Sci, 21, pp.7440~ (2020)
- Herman JP, "Chronic stress plasticity in the hypothalamic paraventricular nucleus", Prog Brain Res, 170, pp.353~364 (2008)
- Kalantaridou SN, "Corticotropin-releasing hormone, stress and human reproduction : an update", J Reprod Immunol, 85, pp.33~39 (2010)
- Elman I, "Common brain mechanisms of chronic pain and addiction", Neuron, 89, pp.11~36 (2016)
- Larauche M, "Corticotropin-releasing factor type 1 receptors mediate the visceral hyperalgesia induced by repeated psychological stress in rats", Am J Physiol Gastrointest Liver Physiol, 294, pp.G1033~G1040 (2008)
- Shimizu T, "Psychological", mental stress-induced effects on urinary function : possible brain molecules related to psychological, Int J Urol, pp.2021, 28[DOI]
- Hanna-Mitchell AT, "Corticotropin-releasing factor family peptide signaling in feline bladder urothelial cells", J Endocrinol, 222, pp.113~121 (2014)
- Marsland AL, "The effects of acute psychological stress on circulating and stimulated inflammatory markers : a systematic review and meta-analysis", Brain Behav Immun, 64, pp.208~219 (2017)
- Wróbel A, "SN003, a CRF1 receptor antagonist, attenuates depressive-like behavior and detrusor overactivity symptoms induced by 13-cis-retinoic acid in rats", Eur J Pharmacol, 812, pp.216~224 (2017)
- Steers WD, "Duloxetine OAB Study Group. Duloxetine compared with placebo for treating women with symptoms of overactive bladder", BJU Int, 100, pp.337~345 (2007)
- Kaneko Y, "Transient receptor potential(TRP)channels : a clinical perspective", Br J Pharmacol, 171, pp.2474~2507 (2014)
- Deruyver Y, "Transient receptor potential channel modulators as pharmacological treatments for lower urinary tract symptoms(LUTS) : myth or reality?", BJU Int, 115, pp.686~697 (2015)
- Drake MJ, "The urinary microbiome and its contribution to lower urinary tract symptoms; ICI-RS 2015", Neurourol Urodyn, 36, pp.850~853 (2017)
- Stamm WE, "Diagnosis of coliform infection in acutely dysuric women", N Engl J Med, 307, pp.463~468 (1982)
- Mansfield KJ, "Urinary tract infection in overactive bladder : an update on pathophysiological mechanisms", Front Physiol, 13, pp.886782~ (2022)
- Pearce MM, "The female urinary microbiome : a comparison of women with and without urgency urinary incontinence", mBio, 5, pp.e01283-14~ (2014)
- Thomas-White KJ, "Incontinence medication response relates to the female urinary microbiota", Int Urogynecol J, 27, pp.723~733 (2016)
- Wu P, "Urinary microbiome and psychological factors in women with overactive bladder", Front Cell Infect Microbiol, 7, pp.488~ (2017)
- Fung TC, "Interactions between the microbiota, immune and nervous systems in health and disease", Nat Neurosci, 20, pp.145~155 (2017)
- Wang XS, "Therapeutic potential of aryl hydrocarbon receptor in autoimmunity", Inflammopharmacology, 28, pp.63~81 (2020)
- Kraneveld AD, "The neuro-immune axis : prospect for novel treatments for mental disorders", Basic Clin Pharmacol Toxicol, 114, pp.128~136 (2014)
- Hodo TW, "Critical neurotransmitters in the neuroimmune network", Front Immunol, 11, pp.1869~ (2020)
- Tyagi P, "Urine cytokines suggest an inflammatory response in the overactive bladder : a pilot study", Int Urol Nephrol, 42, pp.629~635 (2010)
- Compérat E, "Histologic features in the urinary bladder wall affected from neurogenic overactivity--a comparison of inflammation, oedema and fibrosis with and without injection of botulinum toxin type A", Eur Urol, 50, pp.1058~1064 (2006)
- Contreras-Sanz A, "Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria", Am J Physiol Renal Physiol, 311, pp.F805~F816 (2016)
- Gill K, "A prospective observational study of urinary cytokines and inflammatory response in patients with Overactive Bladder Syndrome", BMC Urol, 21, pp.39~ (2021)
- Hypolite JA, "Metabolic studies on rabbit bladder smooth muscle and mucosa", Mol Cell Biochem, 125, pp.35~42 (1993)
- Nemeth CJ, "Changes in canine bladder perfusion with distension", Invest Urol, 15, pp.149~150 (1977)
- Mills KA, "Hypersensitivity of bladder low threshold, wide dynamic range, afferent fibres following treatment with the chemotherapeutic drugs cyclophosphamide and ifosfamide", Arch Toxicol, 94, pp.2785~2797 (2020)
- Dray A, "Inflammatory mediators of pain", Br J Anaesth, 75, pp.125~131 (1995)
- Grundy L, "Histamine induces peripheral and central hypersensitivity to bladder distension via the histamine H1 receptor and TRPV1", Am J Physiol Renal Physiol, 318, pp.F298~F314 (2020)
- Dmitrieva N, "The role of nerve growth factor in a model of visceral inflammation", Neuroscience, 78, pp.449~459 (1997)
- Chuang YC, "The role of bladder afferent pathways in bladder hyperactivity induced by the intravesical administration of nerve growth factor", J Urol, 165, pp.975~979 (2001)
- Clemow DB, "Altered regulation of bladder nerve growth factor and neurally mediated hyperactive voiding", Am J Physiol, 275, pp.R1279~R1286 (1998)
- Nickel C, "The relationship between prostate inflammation and lower urinary tract symptoms : examination of baseline data from the REDUCE trial", Eur Urol, 54, pp.1379~1384 (2008)
- Inamura S, "Upregulation appearance of high endothelial venule-like vessels in benign prostatic hyperplasia is associated with lower urinary tract symptoms", Prostate, 77, pp.794~802 (2017)
- Funahashi Y, "Bladder overactivity and afferent hyperexcitability induced by prostate-to-bladder cross-sensitization in rats with prostatic inflammation", J Physiol, 597, pp.2063~2078 (2019)
- Ni J, "Long-lasting bladder overactivity and bladder afferent hyperexcitability in rats with chemically-induced prostatic inflammation", Prostate, 79, pp.872~879 (2019)
- Pascal LE, "Prostate-specific deletion of Cdh1 induces murine prostatic inflammation and bladder overactivity", Endocrinology, 162, pp.bqaa212~ (2021)
- Igarashi T, "Therapeutic effects of nerve growth factor-targeting therapy for bladder overactivity in rats with prostatic inflammation", Prostate, 81, pp.1303~1309 (2021)
- Sigala S, "Differential gene expression of cholinergic muscarinic receptor subtypes in male and female normal human urinary bladder", Urology, 60, pp.719~725 (2002)
- Bschleipfer T, "Expression and distribution of cholinergic receptors in the human urothelium", Life Sci, 80, pp.2303~2307 (2007)
- Andersson KE, "Urinary bladder contraction and relaxation : physiology and pathophysiology", Physiol Rev, 84, pp.935~986 (2004)
- Finney SM, "Antimuscarinic drugs in detrusor overactivity and the overactive bladder syndrome : motor or sensory actions?", BJU Int, 98, pp.503~507 (2006)
- Drake MJ, "Incidence of urinary retention during treatment with single tablet combinations of solifenacin+tamsulosin OCAS™ for up to 1 year in adult men with both storage and voiding LUTS : a subanalysis of the NEPTUNE", NEPTUNE II randomized controlled studies, 2017, pp.12, e0170726~
- Restorick JM, "The density of cholinergic and alpha and beta adrenergic receptors in the normal and hyper-reflexic human detrusor", Br J Urol, 63, pp.32~35 (1989)
- Stevens LA, "Human idiopathic and neurogenic overactive bladders and the role of M2 muscarinic receptors in contraction", Eur Urol, 52, pp.531~538 (2007)
- Sibley GN, "A comparison of spontaneous and nerve-mediated activity in bladder muscle from man, pig and rabbit", J Physiol, 354, pp.431~443 (1984)
- Takahashi N, "Obstruction alters muscarinic receptor-coupled RhoA", Rhokinase pathway in the urinary bladder of the rat, 2009, pp.28, 257~262
- Krichevsky VP, "Function of M3 muscarinic receptors in the rat urinary bladder following partial outlet obstruction", J Urol, 161, pp.1644~1650 (1999)
- Braverman AS, "Hypertrophy changes the muscarinic receptor subtype mediating bladder contraction from M3toward M2", Am J Physiol Regul Integr Comp Physiol, 285, pp.R701~R708 (2003)
- Andersson KE, "Pharmacological treatment of overactive bladder : report from the International Consultation on Incontinence", Curr Opin Urol, 19, pp.380~394 (2009)
- Stothers L, "A review of the L-arginine-nitric oxide-guanylate cyclase pathway as a mediator of lower urinary tract physiology and symptoms", Can J Urol, 10, pp.1971~1980 (2003)
- McVary KT, "Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia", J Urol, 177, pp.1401~1407 (2007)
- McVary KT, "Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia : a randomized, double-blind trial", J Urol, 177, pp.1071~1077 (2007)
- Stief CG, "A randomised, placebo-controlled study to assess the efficacy of twice-daily vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia", Eur Urol, 53, pp.1236~1244 (2008)
- Filippi S, "Characterization and functional role of androgen-dependent PDE5 activity in the bladder", Endocrinology, 148, pp.1019~1029 (2007)
- Truss MC, "Effects of various phosphodiesterase-inhibitors, forskolin, and sodium ntroprusside on porcine detrusor smooth muscle tonic responses to muscarigenic stimulation and cyclic nucleotide levels in vitro", Neurourol Urodyn, 15, pp.59~70 (1996)
- Joseph S, "Drugs currently undergoing preclinical or clinical trials for the treatment of overactive bladder : a review", Curr Ther Res Clin Exp, 96, pp.100669~ (2022)
- Nishiguchi J, "Suppression of detrusor overactivity in rats with bladder outlet obstruction by a type 4 phosphodiesterase inhibitor", BJU Int, 99, pp.680~686 (2007)
- Kaiho Y, "The effects of a type 4 phosphodiesterase inhibitor and the muscarinic cholinergic antagonist tolterodine tartrate on detrusor overactivity in female rats with bladder outlet obstruction", BJU Int, 101, pp.615~620 (2008)
- Chancellor MB, "Drug Insight : biological effects of botulinum toxin A in the lower urinary tract", Nat Clin Pract Urol, 5, pp.319~328 (2008)
- Kanai A, "Mechanisms of action of botulinum neurotoxins, β3-adrenergic receptor agonists, and PDE5 inhibitors in modulating detrusor function in overactive bladders : ICI-RS 2011", Neurourol Urodyn, 31, pp.300~308 (2012)
- Schulte-Baukloh H, "Botulinum toxin A detrusor injections reduce postsynaptic muscular M2, M3, P2X2, and P2X3 receptors in children and adolescents who have neurogenic detrusor overactivity : a single-blind study", Urology, 81, pp.1052~1057 (2013)
- Cockayne DA, "Urinary bladder hyporeflexia and reduced painrelated behaviour in P2X3-deficient mice", Nature, 407, pp.1011~1015 (2000)
- Apostolidis A, "Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity", J Urol, 174, pp.977~982 (2005)
- Andersson KE, "On the site and mechanism of action of β3-adrenoceptor agonists in the bladder", Int Neurourol J, 21, pp.6~11 (2017)
- Kullmann FA, "Urothelial beta-3 adrenergic receptors in the rat bladder", Neurourol Urodyn, 30, pp.144~150 (2011)
- Coelho A, "Beta-3 adrenergic receptor is expressed in acetylcholine-containing nerve fibers of the human urinary bladder : an immunohistochemical study", Neurourol Urodyn, 36, pp.1972~1980 (2017)
- Eastham J, "The expression of β3-adrenoceptor and muscarinic type 3 receptor immuno-reactivity in the major pelvic ganglion of the rat", Naunyn Schmiedebergs Arch Pharmacol, 388, pp.695~708 (2015)
- Uchida H, "Involvement of cyclic AMP-dependent and-independent mechanisms in the relaxation of rat detrusor muscle via beta-adrenoceptors", Eur J Pharmacol, 518, pp.195~202 (2005)
- Fujimura T, "Expression and possible functional role of the beta3-adrenoceptor in human and rat detrusor muscle", J Urol, 161, pp.680~685 (1999)
- Hicks A, "GW427353(solabegron), a novel, selective beta3-adrenergic receptor agonist, evokes bladder relaxation and increases micturition reflex threshold in the dog", J Pharmacol Exp Ther, 323, pp.202~209 (2007)
- Takeda H, "Effects of beta(3)-adrenoceptor stimulation on prostaglandin E(2)-induced bladder hyperactivity and on the cardiovascular system in conscious rats", Neurourol Urodyn, 21, pp.558~565 (2002)
- ethyl} acetanilide(YM178), a novel selective beta3-adrenoceptor agonist, on bladder function, "J Pharmacol Exp Ther", 2007, 642~647
- Nitti VW, "Urodynamics and safety of the β3-adrenoceptor agonist mirabegron in males with lower urinary tract symptoms and bladder outlet obstruction", J Urol, 190, pp.1320~1327 (2013)
- Michel MC, "β-adrenoceptor agonist effects in experimental models of bladder dysfunction", Pharmacol Ther, 131, pp.40~49 (2011)
- Aizawa N, "Characteristics of the mechanosensitive bladder afferent activities in relation with microcontractions in male rats with bladder outlet obstruction", Sci Rep, 7, pp.7646~ (2017)
- Aizawa N, "Effects of mirabegron, a novel β3-adrenoceptor agonist, on primary bladder afferent activity and bladder microcontractions in rats compared with the effects of oxybutynin", Eur Urol, 62, pp.1165~1173 (2012)
- Andersson KE, "β3-receptor agonists for overactive bladder--new frontier or more of the same?", Curr Urol Rep, 14, pp.435~441 (2013)
- -acetylcholine release experiments in the isolated detrusor, "Eur J Pharmacol", 2015, 115~122
- Silva I, "Inhibition of cholinergic neurotransmission by β3-adrenoceptors depends on adenosine release and A1-receptor activation in human and rat urinary bladders", Am J Physiol Renal Physiol, 313, pp.F388~F403 (2017)
- Nomiya M, "A quantitative analysis of mRNA expression of alpha 1 and beta-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders", J Urol, 170, pp.649~653 (2003)
- Gillespie JI, "Modulation of non-voiding activity by the muscarinergic antagonist tolterodine and the β(3)-adrenoceptor agonist mirabegron in conscious rats with partial outflow obstruction", BJU Int, 110, pp.E132~E142 (2012)
- Biallosterski BT, "Nonvoiding activity of the guinea pig bladder", J Urol, 186, pp.721~727 (2011)
- Kushida N, "On the origin of spontaneous activity in the bladder", BJU Int, 117, pp.982~992 (2016)
- Moro C, "Urothelial", lamina propria spontaneous activity and the role of M3 muscarinic receptors in mediating rate responses to stretch and carbachol, 2011, pp.78, 1442~
- Aizawa N, "Inhibitory effects of vibegron, a β3-adrenoceptor agonist, on the myogenic contractile and mechanosensitive afferent activities in an obstructed rat bladder", Eur J Pharmacol, 933, pp.175272~ (2022)
- Bayrak S, "Does hypercholesterolemia affect the relaxation of the detrusor smooth muscle in rats? In vitro and in vivo studies", Naunyn Schmiedebergs Arch Pharmacol, 388, pp.761~771 (2015)
- Sawada N, "Protective effect of a β3-adrenoceptor agonist on bladder function in a rat model of chronic bladder ischemia", Eur Urol, 64, pp.664~671 (2013)
- Igawa Y, "β3-Adrenoceptors in the normal and diseased urinary bladder-What are the open questions?", Br J Pharmacol, 176, pp.2525~2538 (2019)
- de Groat WC, "Changes in afferent activity after spinal cord injury", Neurourol Urodyn, 29, pp.63~76 (2010)
- Vizzard MA, "Changes in urinary bladder neurotrophic factor mRNA and NGF protein following urinary bladder dysfunction", Exp Neurol, 161, pp.273~284 (2000)
- Kadekawa K, "The role of capsaicin-sensitive C-fiber afferent pathways in the control of micturition in spinal-intact and spinal cord-injured mice", Am J Physiol Renal Physiol, 313, pp.F796~F804 (2017)
- Gotoh D, "Effects of a new β3-adrenoceptor agonist, vibegron, on neurogenic bladder dysfunction and remodeling in mice with spinal cord injury", Neurourol Urodyn, 39, pp.2120~2127 (2020)
- Svalø J, "The novel β3-adrenoceptor agonist mirabegron reduces carbachol-induced contractile activity in detrusor tissue from patients with bladder outflow obstruction with or without detrusor overactivity", Eur J Pharmacol, 699, pp.101~105 (2013)
- Rouget C, "Modulation of nerve-evoked contractions by β3-adrenoceptor agonism in human and rat isolated urinary bladder", Pharmacol Re, 80, pp.14~20 (2014)
- Furuta A, "Additive effects of intravenous and intravesical application of vibegron, a β3-adrenoceptor agonist, on bladder function in rats with bladder overactivity", Naunyn Schmiedebergs Arch Pharmacol, 393, pp.2073~2080 (2020)
- Summers RJ, "Expression of beta 3-adrenoceptor mRNA in rat brain", Br J Pharmacol, 116, pp.2547~2548 (1995)
- Rodriguez M, "Evidence for the presence of beta 3-adrenergic receptor mRNA in the human brain", Brain Res Mol Brain Res, 29, pp.369~375 (1995)
- Ressler KJ, "Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders", Depress Anxiety, 12(Suppl 1), pp.2~19 (2000)
- Tamburella A, "The beta3 adrenoceptor agonist, amibegron(SR58611A)counteracts stress-induced behavioral and neurochemical changes", Eur Neuropsychopharmacol, 20, pp.704~713 (2010)
- Tanyeri P, "Evidence that the anxiolytic-like effects of the beta3 receptor agonist amibegron involve serotoninergic receptor activity", Pharmacol Biochem Behav, 110, pp.27~32 (2013)
- Claustre Y, "Effects of the beta3-adrenoceptor(Adrb3)agonist SR58611A(amibegron)on serotonergic and noradrenergic transmission in the rodent : relevance to its antidepressant", anxiolyticlike profile, 2008, pp.156, 353~364
- Kanno T, "Noradrenaline stimulates ATP release from DRG neurons by targeting beta(3)adrenoceptors as a factor of neuropathic pain", J Cell Physiol, 224, pp.345~351 (2010)
- Zhang X, "Sustained stimulation of β2-and β3-adrenergic receptors leads to persistent functional pain and neuroinflammation", Brain Behav Immun, 73, pp.520~532 (2018)
