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.
Kenney
M A
MA
Amylin Pharmaceuticals, Inc., San Diego, CA 92121.
Moore
C X
CX
Pittner
R
R
Beaumont
K
K
D000262:Adenylyl Cyclases / Q000187:drug effects; D000682:Amyloid / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002116:Calcitonin / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002412:Cations / Q000494:pharmacology; D058228:Islet Amyloid Polypeptide; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018003:Receptors, Calcitonin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012474:Salmon
D000682:Amyloid; D002412:Cations; D058228:Islet Amyloid Polypeptide; D018003:Receptors, Calcitonin; D002116:Calcitonin; D000262:Adenylyl Cyclases; D015740:Calcitonin Gene-Related Peptide