A procedure for measuring alpha 2-adrenergic receptor-mediated inhibition of cyclic AMP accumulation in rat brain slices.

The alpha 2-adrenergic receptor regulation of cyclic adenosine monophosphate (cAMP) accumulation in rat brain slices was examined. using a prelabeling technique for measuring second messenger production. The mixed alpha-adrenergic agonist 6-fluoronorepinephrine, as well as the more selective alpha 2-agonists clonidine and UK-14,304, caused a concentration-dependent inhibition of forskolin-stimulated cAMP accumulation in cerebral cortical slices, whereas phenylephrine, a selective alpha 1-adrenergic agonist, had no inhibitory effect in this system. Moreover, alpha 2-adrenergic receptor antagonists were more potent than alpha 1-adrenergic antagonists in blocking the inhibitory response to UK-14,304. Neither alpha 1- nor alpha 2-adrenergic agonists displayed any inhibitory effect when cAMP accumulation was stimulated by isoproterenol, vasoactive intestinal peptide or 2-chloroadenosine. The results provide further evidence that some alpha 2-adrenergic receptors are negatively coupled to adenylate cyclase in brain, and yield a procedure for studying this phenomenon in intact central nervous system tissue.