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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Poston, L. Aaronson, P. I. Knock, G. A. Sawdy, R. Bennett, P. R. |
| Description | Author Affiliation: Sawdy R ( Department of Obstetrics and Gynaecology, Imperial College School of Medicine, Queen Charlotte's & Chelsea Hospital.) |
| Abstract | The non-steroidal anti-inflammatory drug (NSAID) indomethacin inhibits both constitutive and inducible forms of cyclo-oxygenase (COX-1 and COX-2, respectively), while nimesulide is a selective COX-2 inhibitor. Uterine COX-2 is upregulated before and during term and pre-term labour, and prostaglandins play a crucial role in parturition. We therefore evaluated the effects of these drugs on myometrial contractility and the voltage-gated Ca2+ channel current in tissue strips and isolated human myometrial smooth muscle cells (HMSMC) from myometrial biopsies taken with informed consent from women undergoing caesarean section at term (not in labour). Nimesulide and indomethacin caused almost complete inhibition of spontaneous myometrial contractions at concentrations of 100 and 300 microM, respectively. The Ca2+ channel current was inhibited in a concentration-dependent manner by both drugs, with a 40% reduction of the current at 100 microM nimesulide and 300 microM indomethacin. Nimesulide also accelerated the decay of the Ca2+ channel current. The inhibition of the Ca2+ channel current by 100 microM nimesulide and 300 microM indomethacin was unaffected by the presence of either PGF2alpha or PGE2 (30 microM), and was of similar magnitude whether 10 mM Ba2+ or 1.5 mM Ca2+ was used as the charge carrier. The concentrations of indomethacin and nimesulide required to suppress spontaneous contractility in human pregnant myometrium were much higher than those necessary to inhibit prostaglandin production. The results suggest that both nimesulide and indomethacin inhibit myometrial contractility via mechanisms independent of cyclo-oxygenase inhibition. Blockade of the Ca2+ current may contribute to this effect. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 6 |
| Volume Number | 125 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1998-11-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Anti-Inflammatory Agents, Non-Steroidal Pharmacology Calcium Channel Blockers Calcium Channels Physiology Cyclooxygenase Inhibitors Indomethacin Myometrium Drug Effects Pregnancy Sulfonamides Uterine Contraction In Vitro Techniques Isometric Contraction Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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