Amylin binding in rat renal cortex, stimulation of adenylyl cyclase
and activation of plasma renin.
Wookey, Peter J., Christos Tikellis, He-Cheng Du, Hai-Feng Qin,
Patrick M. Sexton, and Mark E. Cooper.
Department of Medicine, University of Melbourne, Austin &
Repatriation Medical Centre (Repatriation Campus), Heidelberg West,
Victoria 3081, Australia
APStracts 2:0146F, 1995.
ob]125I]-Rat amylin binds to specific sites in the cortex of rat
kidney which can be distinguished from those for [125I]-salmon
calcitonin (sCT) and [125I]-rat a-CGRP on the basis of regional
distribution. These sites have a high affinity (1nM) for amylin, and
[125I]-amylin binding is potently inhibited by the peptide
antagonists, AC413 and sCT8-32, whereas CGRP8-37 is a poor inhibitor
of binding. Furthermore incubation with GTP-[gamma]-S inhibits
[125I]-amylin binding by &GT90%, indicating that binding is
dependent on coupling to G-proteins. In renal cortex, amylin
stimulated adenylyl cyclase activity 3-4 fold, and this was inhibited
by AC413 and sCT8-32 but not by CGRP8-37. Amylin activated plasma
renin two-fold and this was blunted by prior administration of AC413
but not CGRP8-37. 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.
Received 31 May 1995; accepted in final form 15 August 1995.
APS Manuscript Number F173-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.