title: The mechanism underlying the contractile effect of a chemotactic peptide, formyl-Met-Leu-Phe on the guinea-pig Taenia coli.
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.
authors.affiliation: Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawata
authors.forename: Katsuya
authors.initials: K
authors.lastname: Hirano
authors.forename: Junji
authors.initials: J
authors.lastname: Nishimura
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kubo
authors.forename: Hideo
authors.initials: H
authors.lastname: Kanaide
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002630:Chemotactic Factors / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*
chemical_list: D002630:Chemotactic Factors; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium
references.citation: J Neuroimmunol. 2000 Nov 1;111(1-2):102-8
references.pmid: 11063827
references.citation: Immunopharmacol Immunotoxicol. 1999 Aug;21(3):397-419
references.pmid: 10466071
references.citation: Br J Pharmacol. 2001 Jun;133(4):529-38
references.pmid: 11399670
references.citation: Int Immunopharmacol. 2002 Jan;2(1):1-13
references.pmid: 11789660
references.citation: Cell Mol Life Sci. 2002 May;59(5):742-53
references.pmid: 12088275
references.citation: J Biochem. 2002 Jul;132(1):1-6
references.pmid: 12097153
references.citation: Gene. 2002 Oct 16;299(1-2):57-63
references.pmid: 12459252
references.citation: Br J Pharmacol. 2003 Feb;138(4):707-15
references.pmid: 12598425
references.citation: Ann Rheum Dis. 2003 Jun;62(6):501-9
references.pmid: 12759283
references.citation: Mol Cell Biochem. 2003 Jun;248(1-2):105-14
references.pmid: 12870661
references.citation: J Immunol. 1975 Jun;114(6):1831-7
references.pmid: 165239
references.citation: Proc Natl Acad Sci U S A. 1975 Mar;72(3):1059-62
references.pmid: 1093163
references.citation: Proc Natl Acad Sci U S A. 1982 Dec;79(23):7470-3
references.pmid: 6296835
references.citation: J Biol Chem. 1984 May 10;259(9):5430-9
references.pmid: 6371005
references.citation: Prostaglandins. 1984 Jul;28(1):43-56
references.pmid: 6435187
references.citation: J Appl Physiol (1985). 1986 Jan;60(1):141-6
references.pmid: 3944025
references.citation: Br J Pharmacol. 1986 Oct;89(2):349-59
references.pmid: 3096407
references.citation: J Appl Physiol (1985). 1987 Dec;63(6):2450-9
references.pmid: 2893781
references.citation: Am J Physiol. 1989 Jul;257(1 Pt 2):H107-12
references.pmid: 2502028
references.citation: Biochem J. 1990 Oct 15;271(2):515-22
references.pmid: 2173565
references.citation: Br J Pharmacol. 1990 Oct;101(2):273-80
references.pmid: 2257435
references.citation: Biochem Biophys Res Commun. 1992 Apr 30;184(2):582-9
references.pmid: 1374236
references.citation: Genomics. 1992 Jun;13(2):437-40
references.pmid: 1612600
references.citation: J Urol. 1992 Dec;148(6):1944-50
references.pmid: 1331550
references.citation: Am J Physiol. 1993 May;264(5 Pt 1):L475-81
references.pmid: 8498524
references.citation: J Biol Chem. 1993 Aug 25;268(24):18167-75
references.pmid: 8349692
references.citation: J Exp Med. 1995 Jul 1;182(1):207-17
references.pmid: 7540650
references.citation: J Immunol. 1995 Oct 1;155(7):3292-5
references.pmid: 7561021
references.citation: J Neuroimmunol. 1995 Aug;61(1):71-8
references.pmid: 7560015
references.citation: Science. 1996 Jul 12;273(5272):245-8
references.pmid: 8662509
references.citation: J Biol Chem. 1996 Aug 23;271(34):20246-9
references.pmid: 8702756
references.citation: Am J Physiol. 1996 Dec;271(6 Pt 2):H2622-8
references.pmid: 8997324
references.citation: J Mol Cell Cardiol. 1997 Mar;29(3):881-94
references.pmid: 9152849
references.citation: Pharmacol Ther. 1997;74(1):73-102
references.pmid: 9336017
references.citation: Nature. 1997 Oct 30;389(6654):990-4
references.pmid: 9353125
references.citation: Cell Tissue Res. 1998 Apr;292(1):129-35
references.pmid: 9506920
references.citation: J Exp Med. 1998 Apr 20;187(8):1285-94
references.pmid: 9547339
references.citation: Genomics. 1998 Jul 15;51(2):270-6
references.pmid: 9722950
references.citation: J Pharmacol Exp Ther. 1998 Nov;287(2):640-7
references.pmid: 9808691
references.citation: Methods Mol Biol. 1999;114:269-77
references.pmid: 10081024
references.citation: Rev Physiol Biochem Pharmacol. 1999;134:201-34
references.pmid: 10087910
references.citation: Inflamm Res. 2000 Dec;49(12):744-55
references.pmid: 11211928