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Craig E. Crosson, Margaret Petrovich; Contributions of Adenosine Receptor Activation to the Ocular Actions of Epinephrine. Invest. Ophthalmol. Vis. Sci. 1999;40(9):2054-2061.
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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)theophyline
(8-SPT) or the adenosine A2 antagonist
3,7-dimethyl-l-propargylxanthine (DMPX). Epinephrine (500 μg) 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 mm Hg from 1/2 to 1 hour
followed by significant reduction in IOP of 8 to 9 mm Hg from 3 to 5
hours postadministration. These animals also exhibited a significant
increase in PD of 2 to 3 mm from 1/2 to 2 hours
postadministration. Pretreatment with 8-SPT (1000 μg) 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 μg. 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 μl, respectively. Three hours after epinephrine
administration, adenosine and inosine levels had significantly
increased to 11 ± 1.6 and 66 ± 4.4 ng/100 μl,
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.
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