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.
OBJECTIVE
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 pneumatonometry. Adenylyl cyclase activity in homogenates of ciliary processes was assayed ex vivo by measurement of conversion of 32P-alpha-ATP to 32P-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.
Cepelík
J
J
Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Hynie
S
S
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000287:Administration, Topical; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000818:Animals; D002924:Ciliary Body / Q000187:drug effects* / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology; D005280:Fenoterol / Q000008:administration & dosage*; D007429:Intraocular Pressure / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D009798:Ocular Hypertension / Q000139:chemically induced; D009883:Ophthalmic Solutions; D011817:Rabbits; D014065:Tonometry, Ocular; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D009883:Ophthalmic Solutions; D005576:Colforsin; D005280:Fenoterol; D014660:Vasoactive Intestinal Peptide; D000262:Adenylyl Cyclases; D007545:Isoproterenol