Pharmacological Characterization of the CGRP Receptor in the Lateral Line Organ of Xenopus laevis

Abstract

Calcitonin gene-related peptide (CGRP) is a neurotransmitter candidate colocalized with acetylcholine in efferent fibers innervating hair cell organs. We have used the Xenopus laevis lateral line organ to investigate the responses of a hair cell organ to the CGRP family of peptides. Two isoforms of CGRP, rα-CGRP and rβ-CGRP, and a human analog of α-CGRP, h(Tyr°)a–CGRP, produced dose-dependent increases in afferent nerve fiber discharge rate with EC₅₀ values of approximately 1 μM. Rate increases were 31.2, 18.9, and 10.3%, respectively. The peptide fragment rCGRP_8–37 a selective CGRP₁ receptor antagonist, competitively inhibited the response to rα-CGRP. Diacetoamidomethyl cysteine CGRP (r[Cys(ACM)_2,7]α–CGRP), a CGRP₂ agonist, did not change discharge rate. Rat amylin did not increase rate until very high concentrations, and then the change was less than 7%. Rat adrenomedullin produced no increase in rate. Responses to rα-CGRP developed after metamorphosis. No change in spontaneous discharge rate was observed until postmetamorphic day 6, and then it was only 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 CGRP₁ receptor and that CGRP, of the peptides presently known to exist in the CGRP family, is the most likely endogenous peptide mediating these effects.

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