Abstract
The α 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 α-adrenergic agonist 6-fluoronorepinephrine, as well as the more selective α 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 α 1-adrenergic agonists,had no inhibitory effect in this system. Moreover, α 2-adrenergic receptor antagonists were more potent than α 1-adrenergic antagonists in blocking the inhibitory response to UK-14,304. Neither α 1-norα 2-adrenergic antagonists displayed any inhibitory effect when cAMP accumulation was stimulated by isoproterenol, vasoactive intestinal peptide or 2-chloroadenosine. The results provide further evidence that some α 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.
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