van Rossum D, Hanisch U K, Quirion R
Department of Pharmacology, McGill University, Douglas Hospital Research Centre, Verdun, Québec, Canada.
Neurosci Biobehav Rev. 1997 Sep;21(5):649-78. doi: 10.1016/s0149-7634(96)00023-1.
Calcitonin generelated peptide (CGRP) is a neuropeptide discovered by a molecular approach over 10 years ago. More recently, islet amyloid polypeptide or amylin, and adrenomedullin were isolated from human insulinoma and pheochromocytoma respectively, and revealed between 25 and 50% sequence homology with CGRP. This review discusses findings on the anatomical distributions of CGRP mRNA, CGRP-like immunoreactivity and receptors in the central nervous system, as well as the potential physiological roles for CGRP. The anatomical distribution and biological activities of amylin and adrenomedullin are also presented. Based upon the differential biological activity of various CGRP analogs, the CGRP receptors have been classified in two major classes, namely the CGRP1 and CGRP2 subtypes. A third subtype has also been proposed (e.g. in the nucleus accumbens) as it does not share the pharmacological properties of the other two classes. The anatomical distribution and the pharmacological characteristics of amylin binding sites in the rat brain are different from those reported for CGRP but share several similarities with the salmon calcitonin receptors. The receptors identified thus far for CGRP and related peptides belong to the G protein-coupled receptor superfamily. Indeed, modulation of adenylate cyclase activity following receptor activation has been reported for CGRP, amylin and adrenomedullin. Furthermore, the binding affinity of CGRP and related peptides is modulated by nucleotides such as GTP. The cloning of various calcitonin and most recently of CGRP1 and adrenomedullin receptors was reported and revealed structural similarities but also significant differences to other members of the G protein-coupled receptors. They may thus form a new subfamily. The cloning of the amylin receptor(s) as well as of the other putative CGRP receptor subtype(s) are still awaited. Finally, a broad variety of biological activities has been described for CGRP-like peptides. These include vasodilation, nociception, glucose uptake and the stimulation of glycolysis in skeletal muscles. These effects may thus suggest their potential role and therapeutic applications in migraine, subarachnoid haemorrhage, diabetes and pain-related mechanisms, among other disorders.
降钙素基因相关肽（CGRP）是一种10多年前通过分子方法发现的神经肽。最近，胰岛淀粉样多肽或胰淀素以及肾上腺髓质素分别从人胰岛素瘤和嗜铬细胞瘤中分离出来，并显示与CGRP有25%至50%的序列同源性。本综述讨论了CGRP mRNA、CGRP样免疫反应性和受体在中枢神经系统中的解剖分布研究结果，以及CGRP的潜在生理作用。同时还介绍了胰淀素和肾上腺髓质素的解剖分布及生物学活性。基于各种CGRP类似物的不同生物学活性，CGRP受体已被分为两大类，即CGRP1和CGRP2亚型。还提出了第三种亚型（如伏隔核中的亚型），因为它不具有其他两类的药理学特性。大鼠脑中胰淀素结合位点的解剖分布和药理学特征与CGRP报道的不同，但与鲑鱼降钙素受体有一些相似之处。迄今为止鉴定出的CGRP及相关肽的受体属于G蛋白偶联受体超家族。事实上，已有报道称CGRP、胰淀素和肾上腺髓质素在受体激活后可调节腺苷酸环化酶活性。此外，CGRP及相关肽的结合亲和力受GTP等核苷酸调节。已报道了各种降钙素以及最近CGRP1和肾上腺髓质素受体的克隆，结果显示它们与G蛋白偶联受体的其他成员在结构上有相似之处，但也有显著差异。因此，它们可能形成一个新的亚家族。胰淀素受体以及其他假定的CGRP受体亚型的克隆仍有待完成。最后，已描述了多种CGRP样肽的生物学活性。这些活性包括血管舒张、伤害感受、葡萄糖摄取以及刺激骨骼肌中的糖酵解。因此，这些作用可能表明它们在偏头痛、蛛网膜下腔出血、糖尿病和疼痛相关机制等多种疾病中的潜在作用和治疗应用。
