Molecular Pharmacology, Vol 11, 545-551, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Stimulation of Adenosine 3',5'-Monophosphate Formation by Alpha and Beta Adrenergic Agonists in Rat Cerebral Cortical Slices: Effects of Clonidine

¹ National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health, Bethesda, Maryland 20014

Clonidine has no significant effect on basal levels of cyclic 3',5'-AMP in incubated slices of rat cerebral cortex, but this drug and oxymetazoline antagonize norepinerphrine-elicited accumulation of cyclic AMP to a degree which corresponds to the alpha adrenergic component of the norepinephrine response. Phenylephrine has virtually no agonist or antagonist activity in the brain slice system. Clonidine does not antagonize the accumulation of cyclic AMP elicited by maximal concentrations of a beta adrenergic agonist, isoproterenol, and markedly potentiates the stimulatory effects of submaximal concentrations of this agonist. Clonidine completely antagonizes the formation of cyclic AMP elicited by methoxamine, an alpha adrenergic agonist. The results indicate that clonidine and oxymetazoline function as potent antagonists with respect to norepinephrine- and methoxamine-stimulated formation of cyclic AMP in brain tissue, presumably at an alpha adrenergic locus. In addition, clonidine, oxymetazoline, and phenylephrine appear to interact synergistically with the beta adrenergic component of cyclic AMP-generating systems, thus functioning as partial agonists in brain slices under certain conditions.

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ACKNOWLEDGMENT The authors wish to thank Mr. William Padgett and Mrs. Linda Stalvey for excellent technical assistance.