NEUROANATOMICAL LOCALIZATION, PHARMACOLOGICAL CHARACTERIZATION AND FUNCTIONS OF CGRP, RELATED PEPTIDES AND THEIR RECEPTORS

Calcitonin gene-related 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 ins ulinoma and pheochromocytoma respectively, and revealed between 25 and 50% sequence homology with CGRP. This review discusses findings on th e anatomical distributions of CGRP mRNA, CGRP-like immunoreactivity an d receptors in the central nervous system, as well as the potential ph ysiological roles for CGRP. The anatomical distribution and biological activities of amylin and adrenomedullin are also presented. Based upo n the differential biological activity of various CGRP analogs, the CG RP receptors have been classified in two major classes, namely the CGR P(1) and CGRP(2) subtypes. A third subtype has also been proposed (e.g . in the nucleus accumbens) as it does not share the pharmacological p roperties of the other two classes. The anatomical distribution and th e pharmacological characteristics of amylin binding sites in the rat b rain are different from those reported for CGRP but share several simi larities with the salmon calcitonin receptors. The receptors identifie d thus far for CGRP and related peptides belong to the G protein-coupl ed receptor superfamily. Indeed, modulation of adenylate cyclase activ ity following receptor activation has been reported for CGRP, amylin a nd adrenomedullin. Furthermore, the binding affinity of CGRP and relat ed peptides is modulated by nucleotides such as GTP. The cloning of va rious calcitonin and most recently of CGRP I and adrenomedullin recept ors was reported and revealed structural similarities but also signifi cant 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 stil l awaited. Finally, a broad variety of biological activities has been described for CGRP-like peptides. These include vasodilation, nocicept ion, glucose uptake and the stimulation of glycolysis in skeletal musc les. These effects may thus suggest their potential role and therapeut ic applications in migraine, subarachnoid haemorrhage, diabetes and pa in-related mechanisms, among other disorders. (C) 1997 Elsevier Scienc e Ltd.