Escape from vasopressin-induced antidiuresis: role of vasopressin
resistance of the collecting duct.
Ecelbarger, Carolyn A., Chung-Lin Chou, Alanna J. Lee, Susan R.
Digiovanni, Joseph G. Verbalis, and Mark A. Knepper.
Laboratory of Kidney and Electrolyte Metabolism, National Heart,
Lung and Blood Institute, National Institutes of Health, Bethesda,
MD; Division of Nephrology, Dept.of Internal Medicine, Virginia
Commonwealth University, Richmond, VA 23298; Division of
Endocrinology, Georgetown University, Washington D.C. 20007.
APStracts 5:0046F, 1998.
Previously, we demonstrated that escape from vasopressin-induced
antidiuresis ("vasopressin escape") in rats is associated
with a large, selective decrease in whole kidney expression of
aquaporin-2, the vasopressin-regulated water channel. Here, we show
that isolated perfused inner medullary collecting ducts (IMCDs) from
vasopressin-escape rats (dDAVP/water-loaded) have dramatically
reduced vasopressin-dependent osmotic water permeabilities {46% of
control rats (dDAVP alone)} which coincides with a fall in inner
medullary aquaporin-2 protein abundance as measured by immunoblotting
in the opposite kidney. Further, we demonstrate in IMCD suspensions
that cyclic AMP accumulation in response to 1-deamino-[8-D-arginine]
-vasopressin (dDAVP) is substantially reduced in the vasopressin
-escape rats both in the presence and absence of the phosphodiesterase
inhibitor IBMX (3-isobutyl-1-methyl-xanthine). By immunoblotting, we
show that the abundance of two proteins important in cyclic AMP
generation: the stimulatory heterotrimeric G-protein subunit
Gs[alpha] and adenylyl cyclase type VI, do not change. We conclude
that vasopressin escape is associated with relative vasopressin
resistance of the collecting duct cells manifested by decreased
intracellular cyclic AMP levels. The decreased cyclic AMP levels can
contribute to the demonstrated decrease in collecting duct water
permeability in two ways: 1) by causing a decrease in aquaporin-2
expression; and 2) by limiting the acute action of vasopressin to
increase collecting duct water permeability.
Received 9 December 1997; accepted in final form 12 February
1998.
APS Manuscript Number F385-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 19 February 1998