chapter  4
The Binding of CGRP and Adrenomedullin to a Cloned Receptor
BySteve Legon
Pages 10

Calcitonin gene-related pep tide (CGRP) and adrenom edullin (ADM) are m em ­ bers o f a small family o f regulatory peptides w hich is often referred to as the calcitonin family. T his g roup consists o f ca lc iton in (C T), a and β CGRPs, am ylin and ADM though there are indications in the literature suggesting th a t th e re m ig h t be fu r th e r members o f this family yet to be discovered.1'4 This pep tide fam ily is rem arkable in th a t it has been linked w ith th ree o f th e m o st s ig n if ic a n t c o n d itio n s a sso c ia te d w ith age ing -osteopo rosis (C T ), h y p erten s io n (CGRP, ADM) and type 2 diabetes (amylin). A lthough the links m aybe som ew hat te n u ­ ous they canno t be ignored and there has been considerable interest in isolating the receptors for these peptides. D espite this, un til 1991 there had been no repo rt o f the cloning o f a receptor cDNA for any o f these peptides. At that time, a paper was published describing the characterisation o f the pig CT receptor cDNA.5 This paper accompanied one describing a similar receptor, the opos­ sum para thyro id h o rm o n e recep tor6 and slightly followed publication o f the char­ acterisation o f the ra t secretin recep tor.7 A lthough the ir ligands are dissim ilar, these cDNAs are clearly related and define a new class o f seven tra n sm e m b ra n e d o m a in receptors which show no sim ilarity w ith the

previously characterised ‘rhodopsin -like’ receptors beyond possession o f seven tran s­ m em brane dom ains.