Activation of adenylate cyclase by islet amyloid polypeptide with COOH-terminal amide via calcitonin gene-related peptide receptors on rat liver plasma membranes.
Both human and rat islet amyloid polypeptide with COOH-terminal amide (IAPP-NH2) dose-dependently displaced the specific binding of 125I-labeled [Tyr0] rat alpha-calcitonin gene-related peptide (CGRP) to rat liver plasma membranes, whereas human IAPP (IAPP-COOH) had no effect. Conversely, human or rat IAPP-NH2 but not human IAPP-COOH evoked dose-dependent activation of adenylate cyclase in the membranes, and these effects were significantly inhibited by the CGRP-receptor antagonist human CGRP-1(8-37). Moreover, the dose of human or rat IAPP-NH2 necessary for producing half-maximal activation of adenylate cyclase was comparable with that for producing a half-maximal inhibition of the label binding. Thus, IAPP-NH2 but not IAPP-COOH appears to induce adenylate cyclase activation via CGRP receptors on rat liver plasma membranes.
Morishita
T
T
Department of Internal Medicine, Kobe University School of Medicine, Japan.
Yamaguchi
A
A
Fujita
T
T
Chiba
T
T
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D000682:Amyloid; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; C060605:amylinamide; D000262:Adenylyl Cyclases; D015740:Calcitonin Gene-Related Peptide