Abstract
Dose-response curves to leukotrienes B 4 (LTB 4), D 4 (LTD 4), 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, LTD 4 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, LTB 4, LTD 4 and PAF-acether-induced contractions are all dependent on cyclooxygenase. Thromboxane A 2 (TXA 2) could be one of the cyclooxygenase products involved. A part of contractile effects of LTB 4 and LTD 4, but not of histamine, is linked 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.
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