ABSTRACT
T he ca lc iton in fam ily o f pep tides com prises five know n m em bers: calcitonin, am ylin, tw o ca lc iton in-gene-related p ep tides (aC G R P and pCG RP) and ad reno m edullin (ADM ). The calcitonin receptor was cloned in 19911 and it was th o u g h t th a t the receptors for the o ther m em bers o f the pep tid e fam ily w ou ld be sim ilar (as the receptors for op io id pep tides o r chem okines are sim ilar). In 1993 the C alcitoninR ecep to r-L ike R ecep to r, o r CRLR, w as identified .2,3 It has an overall identity to the ca lc ito n in recep to r o f 55% (Fig. 6.1 A). O ther m em bers o f the calcitonin pep tide fam ily were clearly candidate ligands for CRLR b u t it d id no t appear to confer CGRP re c e p to rs o n a n u m b e r o f ce ll l in e s .4 Professor Jan Fischer and D r W alter Born sent us the ir cDNA encoding CRLR to test in oocytes from Xenopus laevis. An advan tage o f expressing receptors in oocytes is that the ir activation can be detected by electrophysiological techn iques. R eceptors th a t activate Gq, mobilise intracellular Ca2+ lead ing to the activation o f an endogenous chlo ride channel and depolarization bu t recep
tors tha t activate Gs or Gi p roduce no electrophysiological response unless exogenous channels are in troduced. The cystic fibrosis transm em brane regulator (CFTR) contains a chloride channel th a t can be activated by receptors tha t couple to Gs or Gi.5 Expres sion o f CRLR in oocytes alone or w ith CFTR produced no new responses to CGRP and we were forced to conclude tha t CRLR did no t encode a CGRP receptor.
