Amylin stimulates proximal tubular sodium transport and cell
proliferation in the rat kidney.
Harris, Peter J., Mark E. Cooper, Siriphun Hiranyachattada, Jennifer
L. Berka, Darren J. Kelly, Michael Nobes, and Peter J. Wookey.
Departments of Medicine[alpha] and Physiology, University of
Melbourne, Austin & Repatriation Medical Centre (Repatriation
Campus) Heidelberg West, Victoria 3081, and Parkville, Victoria 3052,
Australia
APStracts 3:0156F, 1996.
In autoradiographic studies in anesthetised rats [125I]-amylin binding
was associated with proximal convoluted tubules but not distal
tubules, interstitium or glomeruli in the renal cortex. Split-drop
micropuncture experiments showed that perfusion of the peritubular
capillaries with amylin (10-9M) stimulated proximal tubular fluid
absorption by 28%. This effect was inhibited by luminal addition of
ethyl isopropyl amiloride indicating mediation by a brush border
Na+/H+ exchanger. Intravenous infusion of an amylin binding
antagonist, AC187, reduced proximal fluid reabsorption (22%) in
anesthetised rats, indicating a role for endogenous amylin in salt
homeostasis. In primary cultures of rat proximal tubule cells, amylin
(10-7M) stimulated proliferation with a potency equal to epidermal
growth factor. Peptide antagonists (AC187, AC413 and AC512) of the
amylin binding sites in the renal cortex blocked the mitogenic action
of amylin. We conclude that amylin acts on renal proximal tubules to
promote sodium and water reabsorption and cell proliferation. These
novel actions may have implications for the development of
hypertension for example in non-insulin dependent diabetes mellitus
and obesity in which hyperamylinemia has been observed.
Received 6 December 1995; accepted in final form 29 August 1996.
APS Manuscript Number F404-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996