Indomethacin and epinephrine effects on outflow facility and cyclic adenosine monophosphate formation in monkeys.
OBJECTIVE
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 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 micrograms epinephrine, facility increased by approximately 40%, a putatively maximal response, at which time the intracameral epinephrine concentration was approximately 15 microM. 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 micrograms. Doubling the indomethacin dose (250 micrograms) produced no further inhibition, whereas a fivefold larger epinephrine dose (27.5 micrograms) did not overcome the inhibition. Forskolin and epinephrine both stimulated cAMP production in vitro, whereas [indomethacin] > or = 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.
Crawford
K S
KS
Department of Ophthalmology, University of Wisconsin, Madison 53792-3220, USA.
Gange
S J
SJ
Gabelt
B T
BT
Heideman
W
W
Robinson
J C
JC
Hubbard
W C
WC
Kaufman
P L
PL
D000322:Adrenergic Agonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004837:Epinephrine / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007498:Iris / Q000378:metabolism*; D008252:Macaca fascicularis; D009883:Ophthalmic Solutions; D014129:Trabecular Meshwork / Q000187:drug effects / Q000378:metabolism*
D000322:Adrenergic Agonists; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D009883:Ophthalmic Solutions; D005576:Colforsin; D000242:Cyclic AMP; D007213:Indomethacin; D004837:Epinephrine