ABSTRACT
Calcitonin gene related peptide (CGRP) is a sensory neuropeptide w ith po ten t cardiovascular effects tha t include positive ino tro p ic and ch ro n o tro p ic actions, sys tem ic v aso d ila tio n an d h y p o te n s io n in anim als and in m an .1'3 CGRP is d istribu ted th ro u g h o u t th e ce n tra l a n d p e r ip h e ra l n e rv o u s system s an d possesses d iverse b io lo g ica l ac tio n s in c lu d in g reg u la to ry effects o n cen tra l sy m p a th e tic ou tflow , insulin secretion, neuronal differentiation an d en d o th e lia l cell p ro life ra tio n . T he s tra teg ic lo c a tio n o f CG R P w ith in th e senso ry netw orks o f v irtua lly all o rgans suggests a potentia l role for this peptide in diverse physiological and pathophysiological processes. These diverse actions o f CGRP are m ediated by cell surface receptors th a t are specific for CGRP and the ir coupling to the ac tiva tion o f second m essenger systems. Evidence suggests tha t CGRP receptors are coupled to the activation o f adenylyl cyclase through GTP binding proteins (G -proteins) and belong to the ever increasing family o f seven tran sm em brane G -pro te in -coup led re c e p to rs . C G R P re c e p to rs have b ee n id e n tif ied a n d c h a rac te r iz e d in several tissues, including brain, heart, endothelial and vascular sm oo th m uscle cells. These receptors have been classified in to CGRPi and CGRP2 subtypes according to the ph ar macological definition proposed by D ennis
and colleagues.4 The fragm ent CGRP8-37 is a p o te n t a n ta g o n is t a t C G R P i re c e p to rs , w hereas it is a w eak an tag o n is t a t C G R P 2 recep to rs . In a d d itio n , a lin e a r a n a lo g , a c e to a m id o m e th y l c y s te in e 2,7 CG R P ([ CysA C M ] C G R P ), has been re p o rted to be a selective agonist o f CGRP2 receptors in functional assays, b u t has no effect at CGRPi receptors. A lthough func tio n a lly CGRPg.37 an d [CysA CM ]CG RP show d ifferential effects betw een CGRPi and CGRP2 receptors, b o th ligands display equal affinity for in h ib iting [125I] CGRP b in d in g to th e tw o re c e p to rs .5 C G R Pi receptors have been show n to be p resent in lung , kidney, sp leen an d atria . Evidence suggests th a t vas deferens and liver display C G R P2 receptors. A n u m b er o f excellent review artic les have b een p u b lish ed on C G R P a n d its re c e p to r .6' 8 T h is rev iew sum m arizes th e ch a rac te r iza tio n o f th e cloned CG R Pi receptor. R ecent findings from ou r labora to ry have been highlighted in this review.
