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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Nishimura, J. Hirano, K. Ieiri, S. Suita, S. Kanaide, H. |
| Description | Author Affiliation: Ieiri S ( Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi Higashi-Ku, Fukuoka, Japan.) |
| Abstract | 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. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 133 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2001-06-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Calcium Metabolism Colon Drug Effects Leukotriene C4 Pharmacology Muscle Contraction Animals Calcium Channel Blockers Carbachol Cardiotonic Agents Chelating Agents Physiology Diltiazem Drug Interactions Egtazic Acid Guinea Pigs Imidazoles In Vitro Techniques Permeability Type C Phospholipases Comparative Study Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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