Interaction between alpha₂-and beta₂-adrenergic receptors in rabbit ciliary processes

Abstract

The interaction between the alpha₂- and beta₂- adrenergic receptors of ciliary processes has Been studied by examining dose-response curves for adrenergic agonist stimulation of cyclic AMP production by intact, excised rabbit ciliary processes.

Stimulation of cyclic AMP production by 1-isoproterenol is maximum from 0.1 to 1.0 uM; at higher concentrations stimulation decreases and approaches basal levels. Decreased cyclic AMP production at high concentrations of isoproterenol is blocked by the specific alpha₂-adrenergic antagonist, yohimbine, but not by the alpha₁-adrenergic antagonist, prazosin. Ciliary processes from animals after bilateral cervical ganglionectomy also show reduced cyclic AMP production at high concentrations of isoproterenol and this reduction is blocked by yohimbine, but not prazosin. This experiment suggests that the inhibition at high concentrations of isoproterenol is mediated by postsynaptic alpha₂-adrenergic receptors. Cyclic AMP production is relatively insensitive to epinephrine and norepinephrine, but their responces are potentiated by yohimbine.

Catecholamines and clonidine, a specific alpha₂-adrenergic agonist, exhibit dose-dependent inhibition of forskolin-stimulated cyclic AMP production by ciliary processes. I₅₀^s from the dose-response curves are consistent with the characteristic binding affinities of these adrenergic agonists for alpha₂-adrenergic receptors: clonidine = epinephrine > norepinephrine > isoproterenol. Inhibition of forskolin-stimulated cyclic AMP production by clonidine is blocked by yohimbine but not by prazosin.

The dose-response curves for catecholamine stimulation of cyclic AMP production can be understood in terms of the relative affinities of these adrenergic agonists for beta₂- and alpha₂-adrenergic receptors linked to adenylate cyclase via N and N_i respectively. The interaction between these two adrenergic receptors, one which stimulates and one which inhibits stimulation of adenylate cyclase may provide an explanation for some of the paradoxical observations from studies of the effects of catecholamines on aqueous flow.