Comparative effects of drugs on leukotrienes-, PAF-acether- and histamine- induced contractions of guinea-pig lung parenchymal strips.

Dose-response curves to leukotrienes B4 (LTB4), D4 (LTD4), PAF-acether and histamine applied as single or cumulative doses are studied on guinea-pig lung parenchymal strips (GPLP). A mole to mole comparison shows that PAF-acether is the most potent agonist, when GPLP contracts maximally to histamine. GPLP possesses specific receptors to histamine, LTD4 and PAF-acether which can be blocked by selective receptors antagonists: mepyramine as antihistaminic, FPL 55712 as anti-SRS-A substance, BN 52021 and kadsurenone as anti-PAF-receptor antagonists; meanwhile, a part of their action is mediated through the release of arachidonate metabolites. Histamine, LTB4, LTD4 and PAF-acether-induced contractions are all dependent on cyclooxygenase. Thromboxane A2 (TXA2) could be one of the cyclooxygenase products involved. A part of contractile effects of LTB4 and LTD4, but not of histamine, is liked to the generation of lipoxygenase metabolites as their contractions are partially inhibited by NDGA and ETYA. Contraction-induced by PAF-acether is reduced in presence of NDGA but not by FPL 55712, which indicates that lipoxygenase products other than peptidoleukotrienes are involved in the PAF-response.