Pharmacological characterization of the CGRP receptor in the lateral line organ of Xenopus laevis

Calcitonin gene-related peptide (CGRP) is a neurotransmitter candidate colo calized with acetylcholine in efferent fibers innervating hair cell organs. We have used the Xenopus laevis lateral line organ to investigate the resp onses of a hair cell organ to the CGRP family of peptides. Two isoforms of CGRP, r alpha CGRP and r beta -CGRP, and a human analog of alpha -CGRP, h(T yr degrees) alpha -CGRP, produced dose-dependent increases in efferent nerv e fiber discharge rate with EC50 values of approximately 1 muM. Rate increa ses were 31.2, 18.9, and 10.3%, respectively The peptide fragment rCGRP(8-3 7) a selective CGRP(1) receptor antagonist, competitively inhibited the res ponse to r alpha -CGRP. Diacetoamidomethyl cysteine CGRP (r[Cys(ACM)(2,7)] alpha -CGRP), a CGRP(2) agonist, did not change discharge rate. Rat amylin did not increase rate until very high concentrations, and then the change w as less than 7%. Rat adrenomedullin produced no increase in rate. Responses to r alpha -CGRP developed after metamorphosis. No change in spontaneous d ischarge rate was observed until postmetamorphic day 6, and then it was onl y a fraction of the maximal response. This response progressively increased until postmetamorphic day 28, when it reached its maximal value. The most straightforward interpretation of our results is that the effect of CGRP is mediated by the CGRP(1) receptor and that CGRP, of the peptides presently known to exist in the CGRP family, is the most likely endogenous peptide me diating these effects.