Pharmacological identification of the α‐adrenergic receptor type which inhibits the β‐adrenergic activated adenylate cyclase system in cultured astrocytes

The adrenergic agonist norepinephrine can exert its influence on cell function by activating both alpha- and beta-adrenergic receptors. In astrocytes, the alpha-adrenergic receptor activity of norepinephrine is known to inhibit the cyclic AMP response elicited by its action at beta-adrenergic receptors. Pharmacological studies were conducted to identify the subtype of alpha-adrenergic receptor which mediates this inhibitory action. The alpha 2-adrenergic antagonist yohimbine potentiated the cyclic AMP response elicited by norepinephrine, whereas the alpha 1-adrenergic antagonist prazosin did not affect the response. The alpha 2-adrenergic agonist clonidine inhibited the cyclic AMP response elicited by the beta-adrenergic agonist isoproterenol and this inhibition could be blocked by yohimbine but not by prazosin. In contrast, the alpha 1-adrenergic agonist phenylephrine did not inhibit the cyclic AMP response to isoproterenol. These studies indicate that the inhibitory action of norepinephrine is mediated by its action at alpha 2-adrenergic receptors.