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.
Sheykhzade
M
M
Department of Pharmacology, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen O, Denmark.
Nyborg
N C
NC
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004347:Drug Interactions; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000682:Amyloid; D000897:Anti-Ulcer Agents; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D058228:Islet Amyloid Polypeptide; D011943:Receptors, Adrenergic, beta; D018015:Receptors, Calcitonin Gene-Related Peptide; D015237:Dinoprost; D015740:Calcitonin Gene-Related Peptide; D007545:Isoproterenol