The effects of SRS-A and histamine antagonists on antigen-induced contraction of guinea pig trachea

Spirally cut tracheae from actively sensitized guinea pigs were challenged with antigen in the presence and absence of indomethacin. In the absence of indomethacin, the SRS-A antagonist FPL55712, added 30 min before challenge had no effect on antigen-induced contraction (ATC) when added in concentrations less than or equal to 1.7 X 10(-6) M. However with the highest concentration employed (5.2 X 10(-6) M) the duration of ATC was reduced by 45%. Furthermore the enhancement by indomethacin of the peak height of ATC was reduced even by lower (5.2 X 10(-7) M) concentrations of FPL55712. The inhibition of FPL55712 was time-dependent, suggesting that its action was not confined to competitive receptor antagonism. Hence, although our previous data indicate that a lipoxygenase product is involved in ATC, the current findings suggest that lipoxygenase products in addition to SRS-A contribute to the response. THe H1-antagonists mepyramine, chlorpheniramine and diphenhydramine inhibited ATC only in the first minute, and the peak height was reduced only by diphenhydramine. The H2-antagonist cimetidine had no effect on ATC. These data suggest that the contribution of histamine to ATC is small, confined to the first minute following antigen challenge and mediated via H1-receptors. Reduction of the peak height by diphenhydramine may be unrelated to its H1-antagonist properties.