The mechanism underlying the contractile effect of a chemotactic peptide, formyl-Met-Leu-Phe on the guinea-pig Taenia coli

摘要

The contractile mechanism of N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) was investigated in the guinea-pig Taenia coli, by simultaneously monitoring the changes in the cytosolic Ca2+ concentration ([Ca2+]i) and force.fMLP induced a significant elevation of [Ca2+]i and force at concentrations higher than 10 nM. The maximal response was obtained at a concentration of higher than 1 μM.fMLP (10 μM) augmented the force development induced by a stepwise increment of the extracellular Ca2+ concentration during 60 mM K+ depolarization, while it had no effect on the [Ca2+]i elevation, and thus produced a greater force for a given elevation of [Ca2+]i than 60 mM K+ depolarization.The removal of extracellular Ca2+ completely abolished the fMLP-induced contraction. The fMLP-induced [Ca2+]i elevation was inhibited substantially but not completely by 10 μM diltiazem, partly by 10 μM SK&F 96365, and completely by their combination.Y27632, a specific inhibitor of rho-kinase, had no significant effect on the fMLP-induced [Ca2+]i elevation and force development.Chenodeoxycholic acid, a formyl peptide receptor antagonist, specifically abolished the fMLP-induced contraction but not high K+- or carbachol-induced contractions.A dual lipoxygenase/cyclooxygenase inhibitor, a 5-lipoxygenase inhibitor, a nonselective leukotriene receptor antagonist, and a selective type 1 cysteinyl-containing leukotriene receptor antagonist specifically reduced the fMLP-induced contraction.We suggest that the low-affinity-type fMLP receptor and lipoxygenase metabolites of arachidonic acid are involved in the fMLP-induced contraction in the guinea-pig T. coli. This contraction mainly depends on the [Ca2+]i elevation due to Ca2+ influx and the enhancement of Ca2+ sensitivity in the contractile apparatus.