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Am J Physiol Regul Integr Comp Physiol 261: R1242-R1246, 1991;
0363-6119/91 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 261, Issue 5 1242-R1246, Copyright © 1991 by American Physiological Society

ARTICLES

Modulation of vasopressin antidiuretic action by alpha 2-adrenoceptors is species specific

D. P. Brooks, M. Gellai, P. D. DePalma and R. M. Edwards
SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.

There is evidence in the rat that stimulation of renal alpha 2-adrenoceptors modulates vasopressin antidiuretic action and vasopressin-stimulated adenylate cyclase activity. In the present study, we tested the ability of various alpha 2-adrenoceptor agonists to antagonize vasopressin-induced antidiuresis in the conscious hydrated dog and to inhibit vasopressin-induced adenosine 3',5'-cyclic monophosphate (cAMP) generation in rat and dog cortical collecting tubules. Vasopressin infusion (0.01 ng.kg-1.min-1) in five dogs resulted in a decrease in free water clearance from 2.90 +/- 0.42 to -0.34 +/- 0.08 ml/min. The vasopressin receptor antagonist SKF 105494 inhibited this response. Administration of norepinephrine (0.5 microgram.kg-1.min-1) or clonidine (20 micrograms/kg), however, failed to alter the vasopressin-induced antidiuresis. In vitro studies demonstrated that epinephrine caused a dose-dependent reduction in vasopressin-stimulated cAMP levels in cortical collecting tubules from the rat (50% effective concentration 32 nM) but not from the dog. The data indicate that there is a species difference in alpha 2-adrenoceptor modulation of vasopressin action.


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