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

Author:

Gautheron P D1,Coulbault L1,Sugrue M F1

Affiliation:

1. Centre de Recherche, Merck Sharp & Dohme-Chibret, 63203 Riom-Cedex, France

Abstract

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 μg, 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 0ṁ1 μg of PAF. Orally administered indomethacin or BW 755C failed to alter the response to 0ṁ1 μg 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 μg 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 0ṁ1 μg of PAF, a dose as low as 3 μg evoking a significant blockade. The topical administration of 0ṁ1 μg of PAF did not elicit a significant inflammatory reaction and this contrasts with the results obtained after its subconjunctival injection.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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