The combined use of isolated strips of guinea-pig lung parenchyma and ileum as a sensitive and selective bioassay for leukotriene B4 |
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Authors: | Marwa N Samhoun Priscilla J Piper |
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Institution: | Department of Pharmacology Royal College of Surgeons of England London WC2A 3PN, USA |
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Abstract: | The biological effects of leukotriene (LT)B4 were compared, on a molar basis, with those LTC4, LTD4, LTE4, 5-hydroxyeicosatetraenoic acid (5-HETE), PGD2, PGE1, PGF2α, PGI2, 6-oxo-PGF1α, bradykinin (BK) and angiotensin II (Ang II) on isolated strips of guinea-pig lung parenchyma (GPP) and ileum smooth muscle (GPISM) superfused in series.LTB4 similar to LTC4 and LTD4 on GPP, in relation to potency and contractions induced, but differed from LTE4 in being ten times more active and causing contractions of a much shorter duration of action on this tissue. However, unlike the other LTs, LTB4 produced contractions which were resistant to FPL 55712 (1.9μM) and, when given repeatedly, caused tachyphylaxis in GPP,LTB4 was considerable more active on GPP than the other substances investigated. Further, PGD2, PGF2α and PGI2 contracted GPP, the order of potency being PGD2 > PGF2α ? PGI2 whereas PGE1 and PGE2 relaxed this tissue. In contrast to all other agonists tested which contracted GPISM, LTD4 displaying the highest activity, LTB4 was inactive on this tissue. 5-HETE and 6-oxo-PGF1α were inactive on both GPP and GPISM.On the basis of differential effects of LTB4 on GPP and GPISM, this assay repressents a simple and selective means to distinguish LTB4-like materials from other naturally-occuring substances likely to be generated in inflammatory fluids. |
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