The effects of adrenergic agonists on intraocular pressure and on adenylyl cyclase activity of ciliary processes in pigmented rabbits.
The effects of beta-adrenergic agonists isoprenaline, fenoterol and clenbuterol on the activity of adenylyl cyclase from ciliary processes and on intraocular pressure were examined in pigmented rabbits. Isoprenaline, fenoterol and clenbuterol stimulated adenylyl cyclase activity in vitro, but clenbuterol behaved as a partial agonist. Preincubation of ciliary processes with any of these three drugs led to the heterologous desensitization of adenylyl cyclase to the stimulatory effects of beta-adrenergic agonists or vasoactive intestinal peptide (VIP). This desensitization was dose-dependent and was expressed mainly as a decrease of the highest effects of stimulatory drugs. The exact mechanism of this phenomenon is not yet known. After topical administration, all three tested beta-adrenergic agonists decreased intraocular pressure with approximately the same intensity. The relationship between ocular hypotensive effects of beta-adrenergic agonists and their effects on adenylyl cyclase of ciliary processes is discussed. It is concluded that ocular hypotensive effects of adrenergic agonists and other drugs stimulating adenylyl cyclase cannot be explained simply by stimulation or desensitization of adenylyl cyclase of ciliary processes.
Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
J
J
Cepelík
M
M
Dedina
S
S
Hynie
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000287:Administration, Topical; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002924:Ciliary Body / Q000187:drug effects* / Q000201:enzymology*; D002976:Clenbuterol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004351:Drug Resistance; D005280:Fenoterol / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D011817:Rabbits; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D005576:Colforsin; D005280:Fenoterol; D014660:Vasoactive Intestinal Peptide; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D002976:Clenbuterol