Disturbance of peristalsis in the guinea-pig isolated small intestine by indomethacin, but not cyclo-oxygenase isoform-selective inhibitors

摘要

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.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.The COX-1 inhibitor SC-560, the COX-2 inhibitor NS-398 (both at 0.1  – 1 μM) and the isoform-nonselective inhibitors flurbiprofen (0.01 – 10 μM) and piroxicam (0.1 – 50 μM) were without major influence on peristalsis, whereas indomethacin and etodolac (0.1 – 10 μM) disturbed the regularity of peristalsis by causing nonpropulsive circular muscle contractions.Radioimmunoassay measurements showed that SC-560, NS-398, indomethacin and etodolac (each at 1 μM) suppressed the release of 6-keto-prostaglandin F1α (6-keto-PGF1α) from the intestinal segments.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.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.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.