Indomethacin and epinephrine effects on outflow facility and cyclic adenosine monophosphate formation in monkeys

Kathryn S. Crawford, Stephen J. Gange, B'Ann T. Gabelt, Warren Heideman, James C. Robinson, William C. Hubbard, Paul L. Kaufman

Research output: Contribution to journalArticle

Abstract

Purpose. To investigate the effect of indomethacin inhibition of prostanoid production on the epinephrine-stimulated increase in outflow facility and cyclic adenosine monophosphate (cAMP) production in the anterior segment of the monkey eye. Methods. Topical indomethacin was given 1 hour before the intracameral administration of epinephrine to living cynomolgus monkeys. Outflow facility was measured for 45 to 60 minutes, beginning 3 hours after epinephrine administration, by two-level constant pressure perfusion of the anterior chamber. Cyclic adenosine monophosphate formation was measured in cell membranes isolated from rhesus monkey ciliary muscle, ciliary muscle, ciliary processes, trabecular meshwork, and iris in the presence of forskolin, indomethacin, epinephrine, or indomethacin and epinephrine combined. Results. Three hours after the intracameral administration of 5.5 μg epinephrine, facility increased by ~40%, a putatively maximal response, at which time the intracameral epinephrine concentration was ~15 μM. Pretreatment with topical indomethacin produced a dose-dependent inhibition of epinephrine's facility-increasing effect; the maximum inhibition of 50% to 70% occurred at an indomethacin dose of 50 to 125 μg. Doubling the indomethacin dose (250 μg) produced no further inhibition, whereas a fivefold larger epinephrine dose (27.5 μg) did not overcome the inhibition. Forskolin and epinephrine both stimulated cAMP production in vitro, whereas [indomethacin] ≥ 10-4 M partially inhibited both basal and epinephrine-stimulated cAMP production in all four tissues. Conclusions. Approximately half of the epinephrine-induced facility increase is inhibited by indomethacin, but it is unclear whether the indomethacin- inhibitable fraction is mediated by epinephrine-stimulated prostanoid production or release.

Original languageEnglish (US)
Pages (from-to)1348-1359
Number of pages12
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number7
StatePublished - Jun 1 1996

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Keywords

  • aqueous humor outflow facility
  • cyclic adenosine monophosphate
  • epinephrine
  • indomethacin
  • monkey eye

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Crawford, K. S., Gange, S. J., Gabelt, BA. T., Heideman, W., Robinson, J. C., Hubbard, W. C., & Kaufman, P. L. (1996). Indomethacin and epinephrine effects on outflow facility and cyclic adenosine monophosphate formation in monkeys. Investigative Ophthalmology and Visual Science, 37(7), 1348-1359.