체성감각신경세포에서 Vesicular glutamate transporters의 역할
The roles of vesicular glutamate transporters in somatosensory neurons
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초록
글루타메이트(glutamate)는 중추 및 말초신경계에서 중요한 흥분성 신경전달물질이다. Vesicular glutamate transporters (VGLUTs)는 글루타메이트를 시냅스소포(synaptic vesicles)에 충전(packing)하여 세포외유출(exocytotic release)을 한다. VGLUTs는 3개의 서로 다른 형태를 가지고 있으며(VGLUT1, VGLUT2, 그리고 VGLUT3), 이들의 역할은 일차들신경세포(primary afferent neuron)에서 각각 독특한특징을 가지고 있다. 예를 들면 VGLUT1는 Aβ -기계수용기 신경세포(mechanoreceptive neuron)에서 발현이 되며, VGLUT2는 통각수용기 신경세포(nociceptive neuron)에서 발현이 되며, VGLUT3는 C-낮은역치 기계수용기 신경세포(C-low threshold mechanoreceptive neuron)에서 발현이 된다. VGLUT2는 급성(acute) 냉통증(cold pain) 그리고 염증 및 신경손상시 유발되는 통증과민화(pain hypersensitivity)에중요한 역할을 담당한다. 이는 VGLUT2에 의한 글루타메이트 신호전달이 염증 및 신경손상에 의한 통증과민화 전달기전에 관여함을 의미한다. 그러나, 병리학적 상태에서 VGLUT1 및 VGLUT3의 역할에 대해서는 잘 알려져 있지 않다. 본 종설에서는, 최근 발표된 VGLUTs에 관한 연구 결과들과 본 교실에서 발표된 논문들을 바탕으로, VGLUTs가 어떤 성질을 가지고 있는 체성감각신경세포에서 발현되며, 어떤 기능을 담당하고 있는지에 대해서 살펴보고자 한다. 그리하여, 두개안면영역에서 어떠한 형태의 VGLUTs를 통한 글루타메이트 방출이통증 신호전달에 관여하는지에 대한 이해를 돕고자 한다.
Abstract
Glutamate is an important neurotransmitter in the central and peripheral system. The vesicular glutamate transporters (VGLUTs) are involved in the active loading of glutamate into synaptic vesicles before exocytotic release and play an important role in glutamate signaling. There are three isoforms of VGLUTs. VGLUT1 and VGLUT2 are distributed by functionally-distinct subsets of primary sensory neurons: i.e., VGLUT1 is expressed by mostly Aβ mechanoreceptive neurons and VGLUT2 by nociceptive neurons. VGLUT3 is expressed in the C-low threshold mechanoreceptor. However, VGLUT2-dependant glutamate release from primary sensory afferents plays an important role in acute and inflammatory pain, there is little information on the roles of VGLUT1 and VGLUT3 in the pathologic condition. We here review recently published papers in our and others groups showing that VGLUTs-mediated nociceptive information is mediated via specific primary afferent fibers and is processed in a distinct manner and differently in the somatosensory system; it provides us with useful information to better understand processing mechanisms of pain hypersensitivity in the orofacial region.
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