Non‐competitive antagonism of amylin on CGRP1‐receptors in rat coronary small arteries

Abstract
We examined the interaction between rat‐amylin and relaxations induced by rat‐αCGRP and isoprenaline in rat isolated coronary small arteries. Amylin, 0.1–100 nM, had a concentration dependent non‐competitive antagonistic effect on rat‐αCGRP‐induced responses with an EC50 of approximately 1 nM. Amylin did not affect the relaxations induced by isoprenaline at a concentration of 10 nM. The apparent equilibrium dissociation constant, KA, for CGRP1‐receptors in the rat coronary small arteries was approximately 2 nM. Analysis of the relationship between receptor occupancy and response to rat‐αCGRP indicates that the receptor reserve is small. Our results show that amylin in low concentrations acts as a selective non‐competitive inhibitor at CGRP1‐receptors in rat isolated coronary small arteries. British Journal of Pharmacology (2000) 130, 386–390; doi:10.1038/sj.bjp.0703316