AJP - Renal Physiology, Vol 259, Issue 1 1-F8, Copyright © 1990 by American Physiological Society

ARTICLES

Modulation of vasopressin antidiuretic action by renal alpha 2-adrenoceptors

M. Gellai
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.

It has been almost 40 years since the diuretic effect of alpha-adrenoceptor agonists was first demonstrated. Two possible mechanisms were proposed: inhibition of vasopressin secretion and antagonism of the cellular hydrosmotic actions of vasopressin. The debate could not be settled then for the lack of appropriate experimental models and pharmacological tools. Advances made in adrenoceptor pharmacology in the 1970s such as 1) subdivision of alpha-adrenoceptors into alpha 1- and alpha 2-subtypes; 2) development of selective agonists and antagonists; and 3) localization of both adrenoceptor subtypes in the kidney, including the proximal and collecting tubules, stimulated new research. With regard to renal adrenoceptors, selective alpha 2-agonists have been shown to induce diuresis in dogs and rats. Whereas in the dog the increase in urine flow results mostly from an increase in osmolal clearance, in the rat the diuresis results in large part from an increase in the excretion of solute-free water. In vitro studies on isolated collecting tubules from rats and rabbits (none from dogs) have shown that alpha 2-agonists inhibit vasopressin-induced adenosine 3',5'-cyclic monophosphate formation and that this effect is mediated by the inhibitory guanine nucleotide regulatory protein and abolished by pertussis toxin treatment. In vivo evidence in support of such a mechanism was presented from conscious Brattleboro homozygous rats in which a selective alpha 2-agonist inhibited the antidiuretic effect of exogenous vasopressin, and this effect was abolished by pertussis toxin. The physiological importance of renal alpha 2-adrenoceptors was identified by use of adrenal medullectomized rats and the alpha 2-antagonist, yohimbine.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				R. M. Venn and R. M. Grounds Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions{dagger} Br. J. Anaesth., November 1, 2001; 87(5): 684 - 690. [Abstract] [Full Text] [PDF]

				R. G. Menegaz, D. R. Kapusta, H. Mauad, and A. de Melo Cabral Activation of {alpha}2-receptors in the rostral ventrolateral medulla evokes natriuresis by a renal nerve mechanism Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2001; 281(1): R98 - R107. [Abstract] [Full Text] [PDF]

				R. G. Menegaz, D. R. Kapusta, and A. M. Cabral Role of intrarenal alpha 2-adrenoceptors in the renal responses to xylazine in rats Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2000; 278(4): R1074 - R1081. [Abstract] [Full Text] [PDF]

				A. G. Correia, A. C. Madden, G. Bergstrom, and R. G. Evans Effects of Renal Medullary and Intravenous Norepinephrine on Renal Antihypertensive Function Hypertension, April 1, 2000; 35(4): 965 - 970. [Abstract] [Full Text] [PDF]

				A. Junaid, L. Cui, S. B. Penner, and D. D. Smyth Regulation of Aquaporin-2 Expression by the alpha 2-Adrenoceptor Agonist Clonidine in the Rat J. Pharmacol. Exp. Ther., November 1, 1999; 291(2): 920 - 923. [Abstract] [Full Text]

				S. W. Edwards and L. E. Limbird Role for the Third Intracellular Loop in Cell Surface Stabilization of the alpha 2A-Adrenergic Receptor J. Biol. Chem., June 4, 1999; 274(23): 16331 - 16336. [Abstract] [Full Text] [PDF]

				A. D. M. Cabral, D. R. Kapusta, V. A. Kenigs, and K. J. Varner Central alpha 2-receptor mechanisms contribute to enhanced renal responses during ketamine-xylazine anesthesia Am J Physiol Regulatory Integrative Comp Physiol, December 1, 1998; 275(6): R1867 - R1874. [Abstract] [Full Text] [PDF]

				A. Bischoff, W. Rascher, and M. C. Michel Bradykinin may be involved in neuropeptide Y-induced diuresis, natriuresis, and calciuresis Am J Physiol Renal Physiol, October 1, 1998; 275(4): F502 - F509. [Abstract] [Full Text] [PDF]