Amylin binding in rat renal cortex, stimulation of adenylyl cyclase, and activation of plasma renin

Peter J. Wookey, Christos Tikellis, D. U. He-Cheng, Hai Feng Qin, Patrick M. Sexton, Mark E. Cooper

Research output: Contribution to journalArticleResearchpeer-review

61 Citations (Scopus)

Abstract

125 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 a-calcitonin gene-related peptide (α-CGRP) on the basis of regional distribution. These sites have a high affinity (∼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-γS) inhibits I25Iamylin 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.

Original languageEnglish
JournalAmerican Journal of Physiology
Volume270
Issue number2 PART 2
DOIs
Publication statusPublished - 1996
Externally publishedYes

Keywords

  • Calcitonin
  • Calcitonin gene-related peptide
  • Receptor

Cite this