Cyclic-AMP in the aqueous humor: the effects of repeated topical epinephrine administration and sympathetic denervation

Abstract

Cyclic-AMP (c-AMP) may mediate the effects of topical epinephrine on intraocular pressure in the rabbit eye. Experiments which further correlate the decrease in intraocular pressure with the increase in c-AMP in the aqueous humor in response to adrenergic agonists are presented. Repeated, daily topical administration of epinephrine led to diminished responsiveness to this drug on the fifth day. The treated eye demonstrated a smaller decrease in intraocular pressure and a smaller increase in c-AMP in the aqueous humor on the fifth day when compared to the response of a previously untreated eye. Unilateral superior cervical ganglionectomy, after a 2–3-week recovery period, causes a denervation supersensitivity to alpha-adrenergic agonists. Topical norepinephrine and epinephrine caused a greater fall in intraocular pressure and greater increase in c-AMP in the aqueous humor of the denervated eye than of the control eye. The shift to the left of the dose-response curve for epinephrine indicates a greater affinity for agonists in the denervated eye. Intravitreal injections of a high concentration of epinephrine produced a greater maximal response of c-AMP in the aqueous humor of the denervated eye. This is consistent with an increased number of sites for c-AMP production following sympathetic denervation. Speculations on the location of the adenyl cyclase system are discussed.