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

1 Since the cyclo-oxygenase (COX) isoform-nonselective inhibitor indomethac in 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 tr iggered by a rise of the intraluminal pressure and recorded via the pressur e changes associated with peristalsis. 3 The COX-1 inhibitor SC-560, the COX-2 inhibitor NS-398 (both at 0.1 - 1 m uM) and the isoform-nonselective inhibitors flurbiprofen (0.01-10 muM) and piroxicam (0.1-50 muM) were without major influence on peristalsis, whereas indomethacin and etodolac (0.1-10 muM) disturbed the regularity of perista lsis by causing nonpropulsive circular muscle contractions. 4 Radioimmunoassay measurements showed that SC-560, NS-398, indomethacin an d etodolac (each at 1 muM) 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, rela tive to glyceraldehyde-3 phosphate dehydrogenase ribonucleic acid, the expr ession of COX-1 mRNA increased by a factor of 2.0 whereas that of COX-2 mRN A 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 calciu m channels, adenosine triphosphate-sensitive potassium channels or phosphod iesterase 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 i ntestine and that the effect of indomethacin to disturb the regular pattern of propulsive motility in this species is unrelated to COX inhibition.