Abstract
The biological effects of leukotriene (LT)B 4 were compared, on a molar basis, with those LTC 4, LTD 4, LTE 4, 5-hydroxyeicosatetraenoic acid (5-HETE), PGD 2, PGE 1, PGF 2α, PGI 2, 6-oxo-PGF 1α, bradykinin (BK) and angiotensin II (Ang II) on isolated strips of guinea-pig lung parenchyma (GPP) and ileum smooth muscle (GPISM) superfused in series. LTB 4 similar to LTC 4 and LTD 4 on GPP, in relation to potency and contractions induced, but differed from LTE 4 in being ten times more active and causing contractions of a much shorter duration of action on this tissue. However, unlike the other LTs, LTB 4 produced contractions which were resistant to FPL 55712 (1.9μM) and, when given repeatedly, caused tachyphylaxis in GPP, LTB 4 was considerable more active on GPP than the other substances investigated. Further, PGD 2, PGF 2α and PGI 2 contracted GPP, the order of potency being PGD 2 > PGF 2 α ≅ PGI 2 whereas PGE 1 and PGE 2 relaxed this tissue. In contrast to all other agonists tested which contracted GPISM, LTD 4 displaying the highest activity, LTB 4 was inactive on this tissue. 5-HETE and 6-oxo-PGF 1α were inactive on both GPP and GPISM. On the basis of differential effects of LTB 4 on GPP and GPISM, this assay repressents a simple and selective means to distinguish LTB 4-like materials from other naturally-occuring substances likely to be generated in inflammatory fluids.
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