Non-competitive antagonism of amylin on CGRP(1)-receptors in rat coronary small arteries.

We examined the interaction between rat-amylin and relaxations induced by rat-alphaCGRP and isoprenaline in rat isolated coronary small arteries. Amylin, 0.1 - 100 nM, had a concentration dependent non-competitive antagonistic effect on rat-alphaCGRP-induced responses with an EC(50) of approximately 1 nM. Amylin did not affect the relaxations induced by isoprenaline at a concentration of 10 nM. The apparent equilibrium dissociation constant, K(A), for CGRP(1)-receptors in the rat coronary small arteries was approximately 2 nM. Analysis of the relationship between receptor occupancy and response to rat-alphaCGRP indicates that the receptor reserve is small. Our results show that amylin in low concentrations acts as a selective non-competitive inhibitor at CGRP(1)-receptors in rat isolated coronary small arteries.