Effect of topical and intraperitoneal indomethacin on the generation of PGE 2-like activity in rabbit conjunctiva and iris-ciliary body

Abstract

A significant difference was observed in the generation of prostaglandin (PG)E2-like activity between rabbit iris-ciliary body and conjunctiva. The amount of PGE2-like activity produced at any given concentration of arachidonic acid (AA) by the iris-ciliary body was 2–3 times greater than the amount synthesized by the conjunctiva under identical experimental conditions. Also, synthesis of PGE2-like activity was dose-dependent in the iris-ciliary body in the concentration range of 1, 5 and 10 μg AA while in the conjunctiva it was dose-dependent in the concentration range of 10, 50 and 100 μg AA. The effect of indomethacin (INDO) in vivo on the generation of PGE2-like activity in the rabbit conjuctiva and iris-ciliary body was also assessed. Topical INDO (50μl), in concentrations of 0·1%, 0·25% and 0·5%, inhibited the generation of PGE2-like activity from AA in iris-ciliary body and conjunctiva at 2 hr after instillation, respectively. Similarly, intraperitoneal (i.p.) INDO treatment (5 mg/kg, 50mg/kg and 100 mg/kg) inhibited the generation of PGE2-like activity produced from various concentrations of AA in the iris-ciliary body and conjunctiva. However, again a significant difference was observed in the susceptibility of the production of PGE2-like activity to inhibition by INDO between the iris-ciliary body and conjunctiva especially when these tissues were incubated with higher concentrations (>10 μg) of AA. Under these conditions, INDO was less effective in inhibiting PGE2-like activity production in the iris-ciliary body than in the conjunctiva. These results indicate that the substrate concentration is a limiting factor in assessing the inhibitory effects of INDO. However, differences between the distribution of INDO into the anterior uvea and conjunctiva following i.p. or topical pretreatment cannot be excluded. The significance of these findings is discussed.