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

Purpose. The effects of repeated topical administration of the selecti ve beta(2)-adrenergic agonist fenoterol on the intraocular pressure an d on the adenylyl cyclase activity in ciliary processes in rabbit were examined in order to detect their possible causal relationship. Metho ds. Intraocular pressure was measured by pneumatonometry. Adenylyl cyc lase activity in homogenates of ciliary processes was assayed ex vivo by measurement of conversion of P-32-alpha-ATP to P-32-Cyclic AMP. Res ults. A single topical dose of 1% solution of fenoterol elicited a cle ar-cut decrease of the intraocular pressure lasting for several h. Rep eated administration of fenoterol for 2-5 days led to a significant in crease of intraocular pressure, observable from the second to the fift h day. The stimulation of adenylyl cyclase activity ex-vivo by isoprot erenol, vasoactive intestinal polypeptide or forskolin was significant ly decreased on the fifth day (24 h after the administration of the la st dose of fenoterol). Conclusions. Our data showed that repeated topi cal administration of the selective beta(2)-adrenergic agonist increas ed intraocular pressure and desensitized adenylyl cyclase in ciliary p rocesses; if these two effects are related then they would support the idea of direct relationship of decreased cAMP production in ciliary p rocesses to the increase of intraocular pressure, and vice versa. Howe ver, conclusive evidence of this suggestion and of its possible signif icance in another animal species or man would require further study.