The action of platelet activating factor and its antagonism by WEB 2086 on human isolated airways

This study investigated the direct and indirect effects of platelet activating factor (PAF, PAF-acether) on human isolated airways. PAF caused a single non-repeatable contraction which was found to be variable both between lung samples and within tissues from the same lung. The range of contractions induced by PAF, 7 X 10(-8), M and 7 X 10(-7) M was 2-55% and 3-72% of the maximal response to carbachol, respectively. The PAF antagonist WEB 2086, 10(-6) M, inhibited the contraction induced by PAF, 7 X 10(-7) M, (p less than 0.05, n = 5). PAF caused a significant potentiation of the contractile effects of bolus doses of histamine. This potentiation was inhibited by WEB 2086, 10(-6) M, (p less than 0.05, n = 5). These results suggest firstly that the bronchoconstriction observed in man after PAF administration could be the result of an action of PAF on the smooth muscle or result from the action of a second mediator released by PAF from cells within the lung. Secondly, the bronchial hyperresponsiveness observed after PAF administration could be due to a specific alteration in smooth muscle sensitivity. The fact that WEB 2086 inhibited the contractile response to PAF and the potentiation of histamine-induced contraction would suggest that PAF receptors mediate these responses.