The mechanism for the contraction induced by leukotriene C4 in guinea‐pig taenia coli

The mechanism underlying the LTC 4 ‐induced contraction of guinea‐pig taenia coli was determined using the simultaneous measurements of [Ca 2+ ] 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. LTC 4 induced a contraction in the guinea‐pig taenia coli in a concentration‐dependent manner. The maximal response was obtained at 100 n M and the EC 50 value was 5.4±1.9 n M . Both LTC 4 and carbachol induced increases in [Ca 2+ ] i and force. The maximum force induced by 100 n M LTC 4 was significantly smaller than that induced by 10 μ M carbachol, although an increase in [Ca 2+ ] i produced by both agonists was similar. In the permeabilized preparations, carbachol, but not LTC 4 , induced an additional force development at a fixed Ca 2+ concentration. LTC 4 induced no increase in [Ca 2+ ] i and force in the Ca 2+ ‐free solution, while carbachol induced transient increases in both [Ca 2+ ] i and force in a Ca 2+ ‐free solution. Both diltiazem and SK&F 96365 significantly inhibited the LTC 4 − and carbachol‐induced increases in [Ca 2+ ] i and force in normal PSS. The inhibitory pattern of [Ca 2+ ] i by these drugs was also similar. We thus conclude that LTC 4 induces the contraction of the guinea‐pig taenia coli mainly through Ca 2+ influx via both the diltiazem‐sensitive and SK&F 96365‐sensitive Ca 2+ channels, without affecting either the Ca 2+ ‐sensitivity or the intracellular Ca 2+ release. These results indicated that the mechanism underlying the LTC 4 ‐induced contraction differs greatly from that for conventional G‐protein mediated agonists, such as carbachol.British Journal of Pharmacology (2001) 133 , 529–538; doi: 10.1038/sj.bjp.0704122