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Abstract #5399 Published in IGR 1-2
Contributions of adenosine receptor activation to the ocular actions of epinephrine
Crosson CE; Petrovich MInvestigative Ophthalmology and Visual Science 1999; 40: 2054-2061
PURPOSE: Epinephrine is an effective drug for glaucoma treatment. However, the mechanisms responsible for the ocular hypotensive action of this compound are not completely understood. Adenosine is an autacoid released by all cells. This study evaluated the role of adenosine receptor activation in epinephrine-induced changes in ocular function. METHODS: Rabbits were pretreated topically with the moderately selective adenosine A1 antagonist 8- (p-sulfophenyl)theophylline (8-SPT) or the adenosine A2 antagonist 3,7-dimethyl-l-propargylxanthine (DMPX). Epinephrine (500 ?g) was then administered, and intraocular pressures (IOPs), pupil diameters (PDs), or total outflow facility was evaluated. In a separate group of animals, epinephrine or vehicle was administered, and aqueous humor samples obtained to evaluate changes in aqueous humor purine levels by means of high-performance liquid chromatography. RESULTS: In control animals, epinephrine produced a biphasic change in IOP: an initial rise in IOP of approximately 1 mmHg from 1/2 to 1 hour followed by significant reduction in IOP of 8-9 mmHg from 3-5 hours post-administration. These animals also exhibited a significant increase in PD of 2-3 mm from 0.5-2 hours post-administration. Pretreatment with 8-SPT (1000 ?g) enhanced the initial rise in IOP, while significantly inhibiting the ocular hypotensive response. Pretreatment with 8-SPT also significantly enhanced the epinephrine-induced increase in PD. Inhibition of the epinephrine-induced reduction in IOP by 8-SPT was dose-related with an IC50 of 446 ?g. Administration of 8-SPT alone did not significantly alter IOP or PD. The A2 antagonist DMPX did not alter the epinephrine-induced change in IOP or PD. In rabbits pretreated with 8-SPT, the epinephrine-induced increase in outflow facility was significantly reduced by 60% when compared with those in rabbits treated with epinephrine alone. In vehicle-treated rabbits, aqueous humor adenosine and inosine levels were 2.7 ? 0.38 and 29 ? 4.2 ng/100 ?l, respectively. Three hours after epinephrine administration, adenosine and inosine levels had significantly increased to 11 ? 1.6 and 66 ? 4.4 ng/100 ?l, respectively. CONCLUSIONS: These results support the idea that in rabbits epinephrine administration stimulates adenosine release in the anterior segment. This rise in endogenous levels of adenosine then leads to the activation of ocular adenosine receptors and is in part responsible for the ocular hypotensive action of epinephrine.
C.E. Crosson, Department of Ophthalmology and Visual Sciences, Texas Technical University Health Sciences Center, Lubbock, TX; USA
Classification:
11.3.1 Epinephrine (Part of: 11 Medical treatment > 11.3 Adrenergic drugs)
