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

Authors
  • Kawata, Hiroshi
  • Hirano, Katsuya
  • Nishimura, Junji
  • Kubo, Chiharu
  • Kanaide, Hideo
Type
Published Article
Journal
British journal of pharmacology
Publication Date
Jun 01, 2005
Volume
145
Issue
3
Pages
353–363
Identifiers
PMID: 15735654
Source
Medline
License
Unknown

Abstract

1 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 Ca(2+) concentration ([Ca(2+)](i)) and force. 2 fMLP induced a significant elevation of [Ca(2+)](i) and force at concentrations higher than 10 nM. The maximal response was obtained at a concentration of higher than 1 microM. 3 fMLP (10 microM) augmented the force development induced by a stepwise increment of the extracellular Ca(2+) concentration during 60 mM K(+) depolarization, while it had no effect on the [Ca(2+)](i) elevation, and thus produced a greater force for a given elevation of [Ca(2+)](i) than 60 mM K(+) depolarization. 4 The removal of extracellular Ca(2+) completely abolished the fMLP-induced contraction. The fMLP-induced [Ca(2+)](i) elevation was inhibited substantially but not completely by 10 microM diltiazem, partly by 10 microM SK&F 96365, and completely by their combination. 5 Y27632, a specific inhibitor of rho-kinase, had no significant effect on the fMLP-induced [Ca(2+)](i) elevation and force development. 6 Chenodeoxycholic acid, a formyl peptide receptor antagonist, specifically abolished the fMLP-induced contraction but not high K(+)- or carbachol-induced contractions. 7 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. 8 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 [Ca(2+)](i) elevation due to Ca(2+) influx and the enhancement of Ca(2+) sensitivity in the contractile apparatus.

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