Molecular Pharmacology, Vol 14, 1018-1030, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Alpha Adrenergic and Cholinergic-Muscarinic Regulation of Adenosine Cyclic 3',5'-Monophosphate Levels in the Rat Parotid

¹ Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia 22903

(-)-Isoproterenol caused a dose-dependent rise in cyclic AMP concentration in rat parotid slices. Preincubation of rat parotid slices with carbamylcholine or an alpha adrenergic agonist, methoxamine, markedly inhibited the rise of cyclic AMP following stimulation with a beta adrenergic agonist, (-)-isoproterenol. This effect of carbamylcholine was blocked by preincubation with atropine and the effect of methoxamine was blocked by preincubation with phenoxybenzamine. The effects of methoxamine or carbamylcholine were partly reversed by subsequent addition of phentolamine or atropine. Carbamylcholine produced an almost maximal inhibition when added simultaneously with (-)-isoproterenol, while methoxamine required more than 8 min of preincubation to achieve its maximal effect. Carbamylcholine was active either in the absence of exogenous Ca⁺⁺ or in the presence of Ca⁺⁺ and the divalent cation ionophore A23187. Methoxamine was inactive in the absence of added Ca⁺⁺ and failed to reduce further the (-)-isoproterenol stimulated concentrations of cyclic AMP in the presence of Ca⁺⁺ and A23187. Methoxamine, A23187, and carbamylcholine each caused a shift to the right in (-)-isoproterenol dose-response curve. The non-hyperbolicity of the dose response curve to (-)-isoproterenol prevented a simple analysis of the resulting inhibition patterns. Both carbamylcholine and methoxamine produced their effects in the presence of cyclic AMP diesterase inhibitors. Carbamylcholine had little, if any, effect on the rate of disappearance of cyclic AMP. These findings strongly indicate a different mechanism of action for the alpha adrenergic and cholinergic agonists in the rat parotid, which previously have been reported to act via independent receptors, to produce apparently identical physiological and biochemical effects.

Note:
ACKNOWLEDGMENTS We wish to thank Dr. Harper and Dr. Roach for helpful discussion, and Dr. Brooker for the generous gift of the anti-cyclic AMP antibody.

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