Ohki-Hamazaki H
Department of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan.
Prog Neurobiol. 2000 Oct;62(3):297-312. doi: 10.1016/s0301-0082(00)00004-6.
Neuromedin B (NMB) is one of the bombesin (BN)-related peptides in mammals. It was originally purified from pig spinal cords, and it has been shown to be present in central nervous system as well as in gastrointestinal tract. BN and its related peptides have various physiological effects. These include regulation of exocrine and endocrine secretions, smooth muscle contraction, feeding, blood pressure, blood glucose, body temperature and cell growth. NMB exerts its effect by binding to the cell surface receptor. A high affinity receptor, NMB receptor (NMB-R) has been identified. This is a G-protein coupled receptor with seven membrane-spanning regions. Upon agonist binding, several intracellular signaling cascades including phospholipase activation, calcium mobilization and protein kinase C (PKC) activation lead to expression of several genes, DNA synthesis or cellular effects such as secretion. Existence of NMB-R has been demonstrated in several brain regions, notably in olfactory and thalamic regions, and in gastrointestinal tracts. Recent analysis using NMB-R-deficient mice, generated by gene-targeting technique, enables to distinguish functional properties of NMB-R from GRP-R. In this review, molecular characterization, anatomical distribution and pharmacological properties of NMB and NMB-R will be presented. Moreover, physiological roles of NMB and its receptor demonstrated by the analysis of NMB-R-deficient mice will be reported. Comparison with GRP/GRP-R system will provide important information about BN-like peptide systems in mammals.
神经介素B(NMB)是哺乳动物中与蛙皮素(BN)相关的肽类之一。它最初是从猪脊髓中纯化出来的,并且已被证明存在于中枢神经系统以及胃肠道中。BN及其相关肽具有多种生理作用。这些作用包括调节外分泌和内分泌分泌、平滑肌收缩、进食、血压、血糖、体温以及细胞生长。NMB通过与细胞表面受体结合发挥作用。一种高亲和力受体,即NMB受体(NMB-R)已被鉴定出来。这是一种具有七个跨膜区域的G蛋白偶联受体。在激动剂结合后,包括磷脂酶激活、钙动员和蛋白激酶C(PKC)激活在内的几种细胞内信号级联反应会导致多个基因的表达、DNA合成或细胞效应,如分泌。NMB-R已在几个脑区,特别是嗅觉和丘脑区域以及胃肠道中被证实存在。最近利用基因靶向技术生成的NMB-R缺陷小鼠进行的分析,能够区分NMB-R与胃泌素释放肽受体(GRP-R)的功能特性。在这篇综述中,将介绍NMB和NMB-R的分子特征、解剖分布和药理学特性。此外,还将报道通过对NMB-R缺陷小鼠的分析所证明的NMB及其受体的生理作用。与GRP/GRP-R系统的比较将为哺乳动物中类BN肽系统提供重要信息。