Epinephrine increases facility of outflow and cyclic AMP content in the human eye in vitro.
The physiologic mechanism that underlies the epinephrine-induced increase in facility of outflow (C) in glaucomatous human eyes and normal primate eyes is not completely understood. In this study, a recently developed in vitro human eye perfusion model was used to simultaneously monitor facility and cyclic adenosine monophosphate (AMP) changes in response to epinephrine (EPI). In this system, EPI (2.5 x 10(-5) mol/l) resulted in a maximal 44% increase in C, with an ED50 occurring at approximately 8 x 10(-6) mol/l. The C-increasing effect of 10(-5) mol/l EPI was unaffected by 10(-6) mol/l phentolamine. However, it was completely blocked in the presence of 10(-6) mol/l timolol or 2 x 10(-7) mol/l ICI118,551, suggesting the involvement of beta-2 adrenergic receptors. In biochemical studies, 10(-5) mol/l EPI induced a 12- to 14-fold increase in cyclic AMP in the perfusate of treated eyes. This increase was blocked by ICI118,551. In isolated intact human trabecular tissue, a 10 min incubation with 10(-5) EPI stimulated cyclic AMP by a factor of 2.7 over control levels. After 90 min, cyclic AMP levels were increased 4.2 fold over control levels. Collectively, these results show that the intraocular pressure lowering effect of EPI in the human eye is mediated, at least in part, by an increase in facility of outflow. Furthermore, the facility increase appears to be mediated by beta-2 adrenergic receptors and is correlated in time with increased cyclic AMP production.
Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
K A
KA
Erickson-Lamy
J A
JA
Nathanson
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001082:Aqueous Humor / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D010477:Perfusion; D011412:Propanolamines / Q000494:pharmacology; D011863:Radioimmunoassay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013999:Timolol / Q000494:pharmacology; D014129:Trabecular Meshwork / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D013999:Timolol; D000242:Cyclic AMP; D004837:Epinephrine