AJP - Renal Physiology, Vol 266, Issue 1 139-F146, Copyright © 1994 by American Physiological Society

ARTICLES

Vasopressin-independent regulation of collecting duct water permeability

J. S. Han, Y. Maeda, C. Ecelbarger and M. A. Knepper
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.

Studies were conducted in microdissected rat terminal inner medullary collecting duct (IMCD) segments to determine whether agents that activate the phosphoinositide signaling pathway regulate osmotic water permeability independent of the action of vasopressin. Water was withheld from the rats for 24 h before the experiments, a procedure that yields a stably high osmotic water permeability in isolated perfused terminal IMCDs in the absence of vasopressin. In the present studies, the vasopressin-independent osmotic water permeability was sustained at approximately 300 microns/s for at least 90 min. We used the cholinergic agent carbachol (10-100 microM) to activate the phosphoinositide pathway. This agent has previously been reported to increase the hydrolysis of inositol phospholipids in IMCD cells without altering adenosine 3',5'-cyclic monophosphate production. In preliminary studies, we demonstrated (using fura 2) that carbachol transiently increases intracellular calcium and that this response was blocked by atropine, confirming that muscarinic receptors are coupled to activation of the phosphoinositide signaling pathway in these cells. In the absence of vasopressin, both carbachol (10 microM) and phorbol myristate acetate (1 nM) inhibited osmotic water permeability by 40-50% within 10 min. These effects were partially blocked by calphostin C, an inhibitor of protein kinase C. These results demonstrate that activation of phosphatidylinositol hydrolysis and/or activation of protein kinase C markedly inhibits osmotic water permeability in isolated perfused IMCD segments, even in the absence of prior stimulation by vasopressin.

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