Amylin binding in rat renal cortex, stimulation of adenylyl cyclase, and activation of plasma renin.
125I-labeled rat amylin binds to specific sites in the cortex of rat kidney, which can be distinguished from those for 125I-labeled salmon calcitonin (sCT) and 125I-labeled rat alpha-calcitonin gene-related peptide (alpha-CGRP) on the basis of regional distribution. These sites have a high affinity (approximately 1 nM) for amylin, and 125I-amylin binding is potently inhibited by the peptide antagonists AC413 and sCT-(8-32), whereas CGRP-(8-37) is a poor inhibitor of binding. Furthermore, incubation with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) inhibits 125I-amylin binding by > 90%, indicating that binding is dependent on coupling to G proteins. In renal cortex, amylin stimulated adenylyl cyclase activity three- to fourfold, and this was inhibited by AC413 and sCT-(8-32) but not by CGRP-(8-37). Amylin activated plasma renin twofold, and this was blunted by prior administration of AC413 but not CGRP-(8-37). We speculate that amylin may play an important role in renal physiology and that in states of hyperamylinemia, as found in obesity and the insulin resistance syndrome, this peptide may be involved in the genesis and development of hypertension.
Wookey
P J
PJ
Department of Medicine, University of Melbourne, Victoria, Australia.
Tikellis
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Du
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Qin
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Sexton
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Cooper
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D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000682:Amyloid / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002116:Calcitonin / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002678:Chimera; D058228:Islet Amyloid Polypeptide; D007672:Kidney Cortex / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood*; D012474:Salmon
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D002116:Calcitonin; D012083:Renin; D000262:Adenylyl Cyclases; D015740:Calcitonin Gene-Related Peptide