Gewählte Publikation:
Shahbazian, A; Schuligoi, R; Heinemann, A; Peskar, BA; Holzer, P.
Disturbance of peristalsis in the guinea-pig isolated small intestine by indomethacin, but not cyclo-oxygenase isoform-selective inhibitors.
BRIT J PHARMACOL 2001 132: 1299-1309.
Doi: 10.1038/sj.bjp.0703940
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- Führende Autor*innen der Med Uni Graz
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Holzer Peter
- Co-Autor*innen der Med Uni Graz
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Heinemann Akos
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Peskar Bernhard
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Schuligoi Rufina
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- Abstract:
- 1. Since the cyclo-oxygenase (COX) isoform-nonselective inhibitor indomethacin is known to modify intestinal motility, we analysed the effects of COX-1 and COX-2 inhibition on intestinal peristalsis. 2. Peristalsis in isolated segments of the guinea-pig small intestine was triggered by a rise of the intraluminal pressure and recorded via the pressure changes associated with peristalsis. 3. The COX-1 inhibitor SC-560, the COX-2 inhibitor NS-398 (both at 0.1 -- 1 microM) and the isoform-nonselective inhibitors flurbiprofen (0.01 - 10 microM) and piroxicam (0.1 - 50 microM) were without major influence on peristalsis, whereas indomethacin and etodolac (0.1 -- 10 microM) disturbed the regularity of peristalsis by causing nonpropulsive circular muscle contractions. 4. Radioimmunoassay measurements showed that SC-560, NS-398, indomethacin and etodolac (each at 1 microM) suppressed the release of 6-keto-prostaglandin F(1 alpha) (6-keto-PGF(1 alpha)) from the intestinal segments. 5. Reverse transcription - polymerase chain reaction tests revealed that, relative to glyceraldehyde-3 phosphate dehydrogenase ribonucleic acid, the expression of COX-1 mRNA increased by a factor of 2.0 whereas that of COX-2 mRNA rose by a factor of 7.9 during the 2 h experimental period. 6. Pharmacological experiments indicated that the action of indomethacin to disturb intestinal peristalsis was unrelated to inhibition of L-type calcium channels, adenosine triphosphate-sensitive potassium channels or phosphodiesterase type IV. 7. These results show that selective inhibition of COX-1 and COX-2 does not grossly alter peristaltic motor activity in the guinea-pig isolated small intestine and that the effect of indomethacin to disturb the regular pattern of propulsive motility in this species is unrelated to COX inhibition.
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intestinal peristalsis
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cyclo-oxygenase
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prostaglandins
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indomethacin
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flurbiprofen
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piroxicam
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