alpha-Noradrenergic potentiation of neurotransmitter-stimulated cAMP production in rat striatal slices.

The present study examines the possible involvement of alpha-adrenergic receptors in catecholamine-stimulated cAMP production in intact slices of rat striatum. Norepinephrine (NE) produces a greater stimulation of cAMP levels than does the beta-adrenergic agonist, isoproterenol (ISO), and the NE response is inhibited by both the beta-adrenergic antagonist, propranolol, and the alpha-adrenergic antagonist, phentolamine. The alpha-adrenergic agonist, 6-fluoronorepinephrine (6-FNE), has little or no effect on basal cAMP levels; however, 6-FNE causes a marked potentiation of the cAMP response to ISO. Hence, NE stimulation of cAMP levels in striatal slices appears to involve a synergistic interaction between alpha- and beta-adrenergic receptors. alpha-Receptors also potentiate adenosine stimulation of cAMP levels in striatal slices. However, in contrast to results previously reported in cerebral cortical slices, the alpha-adrenergic component of the NE response in striatal slices is not dependent on endogenous adenosine. Finally, 6-FNE interactions with adenylate cyclase in striatal homogenates differ from those observed in the slice preparation. In homogenates, 6-FNE appears to directly stimulate adenylate cyclase through a D-1 receptor. D-1 receptor involvement in catecholamine responses in the striatal slice preparation, on the other hand, appears to be minimal.