Cyclic-AMP in the aqueous humor: The effects of adrenergic agents

Abstract

Adrenergic agents, which reduced intraocular pressure when applied topically to the rabbit eye, increased the cyclic-AMP concentration in the aqueous humor. The order of potency for both reducing intraocular pressure and increasing cyclic-AMP was: epinephrine > norepinephrine > isoproterenol. Intravenous phenoxybenzamine partially blocked the decrease in intraocular pressure and the increase in cyclic-AMP. Intravenous propranolol was ineffective. Topically applied aminophylline, theophylline, and dibutyryl cyclic-AMP were also ineffective. The time course for the epinephrine induced mydriasis was different from the time course for the decrease in intraocular pressure and the increase in cyclic-AMP. The pupil dilated rapidly and then slowly returned to baseline values over the next 4 hr. The intraocular pressure and cyclic-AMP responses peaked at approximately the same time (1·5 hr) and were sustained for at least 5 hr. Substantial tissue levels of cyclic-AMP were found in the cornea, iris-ciliary body and retina-choroid. However, no differences in tissue level could be demonstrated in the control versus epinephrine-treated eye. Thus the site of production of the increased cyclic-AMP in the aqueous humor is not yet resolved. Intracameral injection of high concentrations of cyclic-AMP (estimated final concentration in anterior chamber: 4 × 10 −4 m) caused a marked decrease in intraocular pressure. Similar injections of 5′AMP into the other eye of the same animal were ineffective. The experiments indicate that cyclic-AMP plays a central role in mediating the action of catecholamines on aqueous humor dynamics. The role of the increase in the aqueous humor and possible sites of production and action of the cyclic-AMP are discussed.