INVOLVEMENT OF TACHYKININS IN PLASMA EXTRAVASATION INDUCED BY BRADYKININ AND LOW PH MEDIUM IN THE GUINEA-PIG CONJUNCTIVA

1 The effect of bradykinin, capsaicin, substance P and low pH medium o n plasma extravasation in the guinea-pig conjunctiva has been studied. Evans blue dye was measured in the conjunctiva after local instillati on of the agents into the conjunctival sac. 2 Bradykinin (2-50 nmol), capsaicin (20-50 nmol) and substance P (0.5-5 nmol) caused a dose-depe ndent increase in plasma extravasation with the following order of pot ency: substance P>bradykinin = capsaicin. The effect of capsaicin (50 nmol) and substance P (5 nmol) was abolished by the tachykinin NK1 rec eptor antagonist, CP-99,994 (8 mu mol kg-1, i.v.) (P<0.01), whereas CP -100,263 (8 mu mol kg(-1), i.v.) the inactive enantiomer of CP-99, 994 was without effect. CP-99,994 inhibited by 70% (P<0.01) the effect of bradykinin. 3 The kinin B-2 receptor antagonist, Hoe 140 (icatibant, 10 nmol kg(-1), i.v.) abolished the response to bradykinin (50 nmol) ( P<0.01), but did not affect the responses to capsaicin (50 nmol) or su bstance P (5 nmol). Plasma extravasation induced by low pH medium (pH1 ) was abolished by CP-99,994 (P<0.01) and by Hoe 140 (P<0.01). 4 The p resent findings suggest that: endogenous or exogenous tachykinins incr ease plasma extravasation in the guinea-pig conjunctiva by activation of NK1 receptors; bradykinin-induced plasma extravasation is mediated by tachykinin release from sensory nerve endings; low pH media cause p lasma extravasation via release of kinins that by activation of B-2 re ceptors release tachykinins from sensory nerve endings.