A study of PAF-induced ocular inflammation in the rat and its inhibition by the PAF antagonist, L-652,731

Abstract

A significant inflammatory reaction in the rat conjunctiva followed the subconjunctival injection of synthetic platelet activating factor (PAF) in doses which ranged from 10 ng to 1 microgram, an inflammatory response being evaluated as the increase in both tissue weight and extravasation of Evans blue dye in the conjunctival tissue. Inflammation was still present 6 h after the injection of 0.1 microgram of PAF. Orally administered indomethacin or BW 755C failed to alter the response to 0.1 microgram of PAF. In contrast, the PAF-induced inflammation was blocked by the oral administration of the PAF receptor antagonist, L-652,731, a dose as low as 5 mg kg-1 eliciting a significant inhibition. The topical administration of L-652,731, (two doses of 100 micrograms as a 1% suspension), elicited a slight, but significant blockade of 23%. Its antagonistic action was more striking when it was co-injected subconjunctivally with 0.1 microgram of PAF, a dose as low as 3 micrograms evoking a significant blockade. The topical administration of 0.1 microgram of PAF did not elicit a significant inflammatory reaction and this contrasts with the results obtained after its subconjunctival injection.