Alpha adrenergic and cholinergic-muscarinic regulation of adenosine cycle 3',5'-monophosphate levels in the rat parotid

Y. Oron, J. Kellogg, J. Larner

Research output: Contribution to journalArticlepeer-review

Abstract

(-) 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 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, A 23187, and carbamylcholine each caused a shift to the right in (-) isoproterenol dose-reponse 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 cylic 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.

Original languageEnglish
Pages (from-to)1018-1030
Number of pages13
JournalMolecular Pharmacology
Volume14
Issue number6
StatePublished - 1978
Externally publishedYes

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