1 The effect of bradykinin, capsaicin, substance P and low pH medium on plasma extravasation in the guinea-pig conjunctiva has been studied. Evans blue dye was measured in the conjunctiva after local instillation of the agents into the conjunctival sac.2 Bradykinin (2-50nmol), capsaicin (20-50nmol) and substance P (0.5-5mnmol) caused a dosedependent increase in plasma extravasation with the following order of potency: substance P> bradykinin = capsaicin. The effect of capsaicin (50 nmol) and substance P (5 nmol) was abolished by the tachykinin NKI receptor antagonist, CP-99,994 (8 pmol kg-', i.v.) (P<0.01), whereas CP-100,263 (8 pmol kg-', 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 B2 receptor antagonist, Hoe 140 (icatibant, 10 nmol kg-', i.v.) abolished the response to bradykinin (50 nmol) (P <0.01), but did not affect the responses to capsaicin (50 nmol) or substance P (5 nmol). Plasma extravasation induced by low pH medium (pH 1) was abolished by CP-99,994 (P<0.01) and by Hoe 140 (P<0.01). 4 The present findings suggest that: endogenous or exogenous tachykinins increase plasma extravasation in the guinea-pig conjunctiva by activation of NKI receptors; bradykinin-induced plasma extravasation is mediated by tachykinin release from sensory nerve endings; low pH media cause plasma extravasation via release of kinins that by activation of B2 receptors release tachykinins from sensory nerve endings.
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