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 nM and the EC(50) value was 5.4+/-1.9 nM. Both LTC(4) and carbachol induced increases in [Ca(2+)](i) and force. The maximum force induced by 100 nM LTC(4) was significantly smaller than that induced by 10 microM 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.
Ieiri
S
S
Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi Higashi-Ku, Fukuoka, Japan.
Nishimura
J
J
Hirano
K
K
Suita
S
S
Kanaide
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004110:Diltiazem / Q000494:pharmacology; D004347:Drug Interactions; D004533:Egtazic Acid / Q000494:pharmacology; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D017997:Leukotriene C4 / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D010539:Permeability; D010738:Type C Phospholipases / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D002614:Chelating Agents; D007093:Imidazoles; D017997:Leukotriene C4; D004533:Egtazic Acid; D002217:Carbachol; D010738:Type C Phospholipases; D004110:Diltiazem; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium