The mechanism for the contraction induced by leukotriene C4 in guinea-pig taenia coil

1 The mechanism underlying the LTC4-induced contraction of guinea-pig taenia coli was determined using the simultaneous measurements of [Ca2+](i) and force in whole muscle preparations. Additional experiments were performed in receptor coupled permeabilized preparation. For comparison purposes, the contraction which was induced by a typical G-protein mediated agonist, carbachol was also characterized. 2 LTC4 induced a contraction in the guinea-pig taenia coli in a concentration-dependent manner. The maximal response was obtained at 100 nM and the EC50 value was 5.4 +/- 1.9 nM. 3 Both LTC4 and carbachol induced increases in [Ca2+](i) and force. The maximum force induced by 100 nM LTC4 was significantly smaller than that induced by 10 muM carbachol, although an increase in [Ca2+](i) produced by both agonists was similar. In the permeabilized preparations, carbachol, but not LTC4, induced an additional force development at a fixed Ca2+ concentration. 4 LTC4 induced no increase in [Ca2+](i) and force in the Ca2+-free solution, while carbachol induced transient increases in both [Ca2+](i) and force in a Ca2+-free solution. 5 Both diltiazem and SK&F 96365 significantly inhibited the LTC4- and carbachol-induced increases in [Ca2+](i) and force in normal PSS. The inhibitory pattern of [Ca2+](i) by these drugs was also similar. 6 We thus conclude that LTC4 induces the contraction of the guinea-pig taenia coli mainly through Ca2+ influx via both the diltiazem-sensitive and SK&F 96365-sensitive Ca'' channels, without affecting either the Ca2+-sensitivity or the intracellular Ca2+ release. These results indicated that the mechanism underlying the LTC4-induced contraction differs greatly from that for conventional G-protein mediated agonists, such as carbachol.