Adrenergic regulation of aqueous outflow.
Epinephrine increased outflow facility and cyclic AMP in the in vitro perfused human anterior segment with a maximal facility increase of 44% occurring at approximately 2 x 10(-5) M. Cyclic AMP measured in the perfusate from anterior segments increased by 12-14 fold after administration of 10(-5) M epinephrine. Both the facility increase and cyclic AMP rise were blocked by the beta-2 selective antagonist, ICI118,551. While there was a correlation between the facility increase and elevation in cyclic AMP levels, the rise in cyclic AMP preceded the facility increase by about 1 hour, suggesting that the ultimate effect of epinephrine involved a rather slow event such as synthesis and release of prostaglandins or protein synthesis. Subsequent perfusion studies showed that very large concentrations of indomethacin were necessary to block the outflow facility effect of epinephrine, suggesting that prostaglandin synthesis did not underlie the facility effect in this system. However, 5 x 10(-5) M cyclohexamide blocked the effect on outflow facility of both epinephrine and forskolin, but did not block the rise in cyclic AMP. These studies suggest that protein synthesis may play a role in the epinephrine-induced facility increase at some point beyond the second messenger level.
Erickson
K
K
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston.
Liang
L
L
Shum
P
P
Nathanson
J A
JA
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000869:Anterior Eye Segment / Q000187:drug effects / Q000378:metabolism*; D001082:Aqueous Humor / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D010477:Perfusion; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D003513:Cycloheximide; D000242:Cyclic AMP; D004837:Epinephrine