Corleto V D, Nasoni S, Panzuto F, Cassetta S, Delle Fave G
Department of Digestive and Liver Diseases, II School of Medicine and Surgery, University of La Sapienza, S. Andrea Hospital, Via di Grottarossa 1035, 00189 Rome, Italy.
Dig Liver Dis. 2004 Feb;36 Suppl 1:S8-16. doi: 10.1016/j.dld.2003.11.008.
The heptahelical receptor superfamily constitutes the largest single family of transmembrane-signalling molecules that regulate a wide range of physiological processes. The five somatostatin receptors represent a distinct subgroup of this seven transmembrane receptor superfamily. They range in size from 356 to 391 amino acids with 39-57% protein identity between the subtypes with 100 residues strictly conserved among the somatostatin receptor sequences. A high grade of mRNA homology exists in somatostatin receptor subtypes cloned from different species. Following somatostatin receptor binding and functional activity studies, two alternative models of ligand-binding interaction have been hypothesised. One relies on the presence of a binding pocket within the receptor structure constituted by specific amino acids residues, the other denies the presence of such binding structures and suggests that it is the interaction of agonists with specific extracellular and/or transmembrane domains that determine stable receptor structure conformation. Somatostatin receptors, as, indeed, all G-protein-coupled receptors are able to regulate their responsiveness to agonist exposure. This agonist-specific regulation includes three main events, namely, desensitisation, receptor internalisation and receptor degradation. The cell expression of somatostatin receptor subtypes, at the mRNA level, has been characterised in rodent and in human organs with multiple subtype expression in brain and peripheral tissues.
七螺旋受体超家族是调节多种生理过程的跨膜信号分子中最大的单一家族。五种生长抑素受体代表了这个七跨膜受体超家族中的一个独特亚组。它们的大小从356到391个氨基酸不等，各亚型之间的蛋白质同源性为39 - 57%，生长抑素受体序列中有100个残基严格保守。从不同物种克隆的生长抑素受体亚型存在高度的mRNA同源性。在生长抑素受体结合和功能活性研究之后，人们提出了两种配体结合相互作用的替代模型。一种模型依赖于受体结构内由特定氨基酸残基构成的结合口袋的存在，另一种模型则否认这种结合结构的存在，并认为是激动剂与特定细胞外和/或跨膜结构域的相互作用决定了稳定的受体结构构象。实际上，生长抑素受体和所有G蛋白偶联受体一样，都能够调节它们对激动剂暴露的反应性。这种激动剂特异性调节包括三个主要事件，即脱敏、受体内化和受体降解。生长抑素受体亚型在mRNA水平的细胞表达已在啮齿动物和人类器官中得到表征，在脑和外周组织中存在多种亚型表达。
