Inhibitory effects of clonidine and dopamine on adenylate cyclase of rabbit ciliary processes.

The inhibitory effects of the alpha 2-adrenergic agonist clonidine and that of dopamine were studied on the adenylate cyclase activity in homogenates of ciliary processes. Clonidine inhibited in a dose-dependent manner basal adenylate cyclase activity as well as that stimulated by isoproterenol or forskolin. However, the adenylate cyclase activity stimulated by isoproterenol was sensitive to at least one order lower inhibitory concentrations of clonidine than basal or forskolin-stimulated adenylate cyclase. Dopamine inhibited adenylate cyclase stimulated by isoproterenol considerably less potently than clonidine. The slope of the dopamine dose-response curve was, however, similar to that of the dose-response curve of clonidine. The inhibitory effects of clonidine and dopamine were antagonized by an alpha 2-adrenergic antagonist, yohimbine, in a manner suggesting a competitive nature of this interaction. On the contrary, the inhibitory effects of neither clonidine nor dopamine were prevented by an alpha 1-adrenergic antagonist, prazosin. In addition, the effect of dopamine was not antagonized by the D2-antagonist, tiapride. Taken together, these results strongly indicate that both clonidine and dopamine exert their inhibitory effects by the stimulation of alpha 2-adrenergic receptors. Accordingly, they provide experimental evidence that both basal and drug-stimulated adenylate cyclase activity of ciliary processes can be inhibited via stimulation of alpha 2-adrenergic receptors. The substantially higher sensitivity of isoproterenol-stimulated than basal or forskolin stimulated adenylate cyclase to alpha 2-adrenergic inhibition seems to be a unique feature of this enzyme of ciliary processes. It is suggested that this may reflect an involvement of alpha 2-adrenergic receptors in the physiological feedback mechanism preventing the over-stimulation of adenylate cyclase of ciliary processes during excessive adrenergic drive.