Extracellular nucleotide receptor inhibits avp-stimulated water
permeability in inner medullary collecting duct.
Kishore, Bellamkonda K., Chung-Lin Chou, and Mark A. Knepper.
Laboratory of Kidney and Electrolyte Metabolism, National Heart,
Lung and Blood Institute, National Institutes of Health, Bethesda,
Maryland 20892
APStracts 2:0122F, 1995.
The P2u class of nucleotide receptors is linked to mobilization of
intracellular Ca++ in many cell types including the renal collecting
duct cells. In the present studies we examined the effects of
nucleotides (ATP, UTP & ADP; 10 [mu]M each) on the AVP (0.1 nM)
stimulated osmotic water permeability (Pf) in in vitro per fused
terminal inner medullary collecting ducts (t-IMCD) of rat. ATP or UTP
when added to the bath, decreased the AVP-stimulated Pf by about 40%.
These effects were reversible upon withdrawal of the nucleotides.
However, addition of ADP to the bath or sham exchange of the bath had
no significant effect on the Pf. Fur ther, ATP did not have any
significant effect on the Pf stimulated either by a membrane
permeant, non-hydrolyzable cAMP analog [8-(4-chlorophenylthio)-cAMP
(0.1 mM) or by forskolin (1 [mu]M). In line with these findings, ATP
decreased the AVP-stimulated cAMP levels in IMCD suspensions to about
68%. In addition, ATP did not exert an inhibitory effect on the AVP
-stimulated Pf in the presence of calphostin C (150 nM), an inhibitor
of protein kinase C. These results lead us to conclude that: (i)
agonist occupancy of the putative nucleotide receptor in the t-IMCD
causes an inhibition of AVP-stimulated Pf; and (ii) this effect is
due to a decrease in cellular cAMP levels, most likely resulting from
activation of the phosphoinositide signaling pathway.
Received 16 February 1995; accepted in final form 10 July 1995.
APS Manuscript Number F59-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.