Salmon calcitonin binding and stimulation of cyclic AMP generation in rat skeletal muscle.

Salmon calcitonin potently competes for amylin binding sites in rat brain and has amylin-like actions upon glucose metabolism in rat muscle. We report here that [125I]-salmon calcitonin binds to rat hindlimb muscle membranes with high affinity (Kd = 0.47 pM). Binding was inhibited by rat amylin (Ki = 2 nM), rat alpha CGRP (Ki = 8 nM), rat beta CGRP (Ki = 11 nM), and rat calcitonin (Ki = 64 nM). Binding was maximal when measured in a hypotonic NaHepes buffer, and was significantly reduced in affinity when salts of Mg++, Ca++, Na+ or K+ were present. Incubation of rat hindlimb muscle membranes with salmon calcitonin at concentrations of 10 pM and above stimulated cyclic AMP generation. These results describe a skeletal muscle binding site which may mediate some of the actions of exogenous salmon calcitonin and of endogenous amylin and related peptides upon skeletal muscle fuel metabolism.