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

Abstract

The interaction between the alpha 2- and beta 2-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 microM; at higher concentrations stimulation decreases and approaches basal levels. Decreased cyclic AMP production at high concentrations of isoproterenol is blocked by the specific alpha 2-adrenergic antagonist, yohimbine, but not by the alpha 1-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 alpha 2-adrenergic receptors. Cyclic AMP production is relatively insensitive to epinephrine and norepinephrine, but their responses are potentiated by yohimbine. Catecholamines and clonidine, a specific alpha 2-adrenergic agonist, exhibit dose-dependent inhibition of forskolin-stimulated cyclic AMP production by ciliary processes. I50s from the dose-response curves are consistent with the characteristic binding affinities of these adrenergic agonists for alpha 2-adrenergic receptors: clonidine = epinephrine greater than norepinephrine greater than isoproterenol. Inhibition of forskolin-stimulated cyclic AMP production by clonidine is blocked by yohimbine but not by prazosin.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of Adenylate Cyclase in Bovine Ciliary Process and Rabbit Iris Ciliary Body to Alpha2-Adrenergic Agonists

“…By adenine labelling (7), they have demonstrated that the stimulation of the ct2-receptors results in an inhibition of cyclic AMP production. Further investigations have confirmed that ct2-adrenoceptors are negatively coupled to adenylate cyclase in ICB of rabbit, and probably via a GTP binding protein, Gi (8)(9).…”

“…Using an adenine labelling technique, Mittag et al, (7) found that adenylate cyclase of the ICB was also coupled to inhibitory receptors, which appeared to be cc2-adrenergic receptors. More recently, interaction between the CC2 and ß2-adrenergic receptors and characterization of oa-adrenergic receptors negatively coupled to adenylate cyclase in rabbit ciliary processes have been described (8)(9). These investigations demonstrated that adrenergic control of adenylate cyclase through negative coupling of ct2-adrenergic receptors occurs in rabbit ciliary process.…”

Effect of ß-adrenergic agents on intracellular potential of rabbit ciliary epithelium

“…Interactions between the two adrenergic systems have been observed during transepithelial studies on the isolated I-CB (21) and in the peripheral nervous system (22,23). Interactions have also been shown using ligand binding studies on rabbit I-CB (10,24) and protein kinase C activation in rat pinealocytes (25). Although our data does not permit identification of the precise site of this ␣-␤ interaction, we believe it may occur at the level of agonist binding to the cell membrane receptors, at the second messenger signaling, or with gating of the transport proteins in the ciliary epithelium.…”

Effects of Topical Epinephrine on Aqueous Humor Dynamics in the Cat

“…It is recognized that α-and β-adrenergic receptors in the ciliary body (Bausher, Gregory and Sears, 1987 ;Jin, Verstappen and Yorio, 1994 ;Mittag and Tormay, 1985 ;Neufeld and Page, 1977) and trabecular meshwork (Jampel et al, 1987) play an important role in regulating aqueous humor dynamics. Epinephrine is a potent agonist of both α-and β-receptors, and its effects are thus rather complex.…”