SHORT COMMUNICATION: Repeated topical administration of fenoterol in rabbit reverses its initial ocular hypotensive effect and decreases sensitivity of adenylyl cyclase in ciliary processes to stimulatory agents

Abstract

PURPOSE. The effects of repeated topical administration of the selective beta 2 -adrenergic agonist fenoterol on the intraocular pressure and on the adenylyl cyclase activity in ciliary processes in rabbit were examined in order to detect their possible causal relationship. METHODS. Intraocular pressure was measured by pneuma-tonometry. Adenylyl cyclase activity in homogenates of ciliary processes was assayed ex vivo by measurement of conversion of 32 P-alpha-ATP to 32 P-cyclic AMP. RESULTS. A single topical dose of 1% solution of fenoterol elicited a clear-cut decrease of the intraocular pressure lasting for several h. Repeated administration of fenoterol for 2–5 days led to a significant increase of intraocular pressure, observable from the second to the fifth day. The stimulation of adenylyl cyclase activity ex vivo by isoproterenol, vasoactive intestinal polypeptide or forskolin was significantly decreased on the fifth day (24 h after the administration of the last dose of fenoterol). CONCLUSIONS. Our data showed that repeated topical administration of the selective beta 2 -adrenergic agonist increased intraocular pressure and desensitized adenylyl cyclase in ciliary processes; if these two effects are related then they would support the idea of direct relationship of decreased cAMP production in ciliary processes to the increase of intraocular pressure, and vice versa. However, conclusive evidence of this suggestion and of its possible significance in another animal species or man would require further study.