Role of Nicotinic Acetylcholine Receptor α3 and α7 Subunits in Detrusor Overactivity Induced by Partial Bladder Outlet Obstruction in Rats
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Purpose: To investigate the role of α3 and α7 nicotinic acetylcholine receptor subunits (nAChRs) in the bladder, using a ratmodel with detrusor overactivity induced by partial bladder outlet obstruction (BOO). Methods: Forty Sprague-Dawley rats were used: 10 were sham-operated (control group) and 30 were observed for 3 weeks afterpartial BOO. BOO-induced rats were further divided into 3 groups: Two groups of 10 rats each received intravesicular infusionswith hexamethonium (HM group; n=10) or methyllycaconitine (MLC group; n=10), which are antagonists for α3and α7 nAChRs, respectively. The remaining BOO-induced rats received only saline infusion (BOO group; n=10). Based onthe contraction interval measurements using cystometrogram, the contraction pressure and nonvoiding bladder contractionswere compared between the control and the three BOO-induced groups. Immunofluorescent staining and Western blottingwere used to analyze α3 and α7 nAChRs levels. Results: The contraction interval of the MLC group was higher than that of the BOO group (P<0.05). Nonvoiding bladdercontraction almost disappeared in the HM and MLC groups. Contraction pressure increased in the BOO group (P<0.05)compared with the control group and decreased in the HM and MLC groups compared with the BOO group (P<0.05). Immunofluorescencestaining showed that the α3 nAChR signals increased in the urothelium, and the α7 nAChR signals increasedin the urothelium and detrusor muscle of the BOO group compared with the control group. Western blot analysisshowed that both α3 and α7 nAChR levels increased in the BOO group (P<0.05). Conclusions: Alpha3 and α7 nAChRs are associated with detrusor overactivity induced by BOO. Furthermore, nAChR antagonistscould help in clinically improving detrusor overactivity.
Abstract
Purpose: To investigate the role of α3 and α7 nicotinic acetylcholine receptor subunits (nAChRs) in the bladder, using a ratmodel with detrusor overactivity induced by partial bladder outlet obstruction (BOO). Methods: Forty Sprague-Dawley rats were used: 10 were sham-operated (control group) and 30 were observed for 3 weeks afterpartial BOO. BOO-induced rats were further divided into 3 groups: Two groups of 10 rats each received intravesicular infusionswith hexamethonium (HM group; n=10) or methyllycaconitine (MLC group; n=10), which are antagonists for α3and α7 nAChRs, respectively. The remaining BOO-induced rats received only saline infusion (BOO group; n=10). Based onthe contraction interval measurements using cystometrogram, the contraction pressure and nonvoiding bladder contractionswere compared between the control and the three BOO-induced groups. Immunofluorescent staining and Western blottingwere used to analyze α3 and α7 nAChRs levels. Results: The contraction interval of the MLC group was higher than that of the BOO group (P<0.05). Nonvoiding bladdercontraction almost disappeared in the HM and MLC groups. Contraction pressure increased in the BOO group (P<0.05)compared with the control group and decreased in the HM and MLC groups compared with the BOO group (P<0.05). Immunofluorescencestaining showed that the α3 nAChR signals increased in the urothelium, and the α7 nAChR signals increasedin the urothelium and detrusor muscle of the BOO group compared with the control group. Western blot analysisshowed that both α3 and α7 nAChR levels increased in the BOO group (P<0.05). Conclusions: Alpha3 and α7 nAChRs are associated with detrusor overactivity induced by BOO. Furthermore, nAChR antagonistscould help in clinically improving detrusor overactivity.
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