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Some effects of leukotriene D 4 on the mechanical properties of the guinea‐pig basilar artery
Author(s) -
Nishiye Eiichiro,
Itoh Takeo,
Kuriyama Hirosi
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb10315.x
Subject(s) - muscle contraction , contraction (grammar) , endothelium , acetylcholine , guanethidine , chemistry , methysergide , endocrinology , nitroarginine , medicine , leukotriene d4 , nitric oxide , antagonist , nitric oxide synthase , receptor , stimulation
1 The effects of leukotriene D 4 (LTD 4 ) on the mechanical properties of smooth muscle cells from the guinea‐pig basilar artery were investigated in whole and chemically skinned muscle strips. 2 In strips with an intact endothelium, 5‐hydroxytryptamine (5‐HT; 10 μM), LTD 4 and LTC 4 (1 μM), STA 2 (1 n m ‐10n m ) and high K + (30 m m ‐128m m ) generated contractions. These comprised an initial phasic and subsequently generated tonic response with different amplitudes. Acetylcholine (ACh, 0.1–10 μ m ) inhibited and methylene blue (1–10 μ m ) enhanced the tonic component of these contractions in endothelium‐intact muscle strips. In endothelium‐denuded tissues, methylene blue had no effect on mechanical responses and ACh produced a further contraction in the presence of LTD 4 . 3 When the endothelium was removed, the amplitude of contractions induced by all tested stimulants markedly increased. In intact muscle strips, the order of potency for the production of a maximum response was; 128 m m K + > STA 2 > LTD 4 = LTC 4 = 5‐HT. Following removal of the endothelium; STA 2 > 128 m m K + > LTD 4 = LTC 4 ≤ 5‐HT. 4 In endothelium‐denuded strips, the selective LTD 4 antagonists, ONO‐RS‐411 and FPL 55712 inhibited the LTD 4 ‐induced contraction. In contrast, guanethidine, prazosin, yohimbine, atropine and mepyramine had no effect. Indomethacin and a thromboxane A 2 (TXA 2 ) antagonist, ONO‐3708 also had no effect on LTD 4 ‐induced contractions in endothelium‐denuded strips. 5 In endothelium‐denuded strips, nifedipine inhibited the tonic contraction induced by LTD 4 but not the phasic component. In Ca 2+ ‐free solution containing 2 m m EGTA, LTD 4 produced only the phasic contractions. 6 In saponin‐treated chemically skinned muscle strips, LTD 4 had no effect on either the pCa‐tension relationship or on the release of Ca 2+ from intracellular stores. However, inositol 1,4,5‐trisphosphate released Ca 2+ from the stores and 1,2‐diolein, an activator of protein kinase C, enhanced the contractions induced by 0.3 μm m Ca 2+ . 7 It was concluded that LTD 4 acts on both the endothelium and on the smooth muscle cells of the guinea‐pig basilar artery. It stimulates the release of endothelium‐derived relaxing factor (EDRF) which tends to inhibit the LTD 4 ‐induced contraction. It also interacts with receptors on the smooth muscle and produces a contraction as a result of an increase in both voltage‐dependent and receptor‐activated Ca 2 influx and, in part, the release of Ca 2 + from cellular storage sites.