THE EFFECT OF INDOMETHACIN ON THE RELEASE OF PROSTAGLANDIN E<sub>2</sub> AND ACETYLCHOLINE FROM GUINEA‐PIG ISOLATED ILEUM AT REST AND DURING FIELD STIMULATION

3 Aspirin (20-100 Rtg/ml) or indomethacin (1-4 ±g/ml) applied serosally greatly inhibited all aspects of peristalsis in guinea-pig ileum and colon. Inhibition of peristalsis of the ileum by aspirin was antagonized by prostaglandin E2 and that by indomethacin was removed by prostaglandin F2a or ACh. Inhibition of colonic peristalsis by aspirin was antagonized by prostaglandin E2 but rarely by ACh, and that by indomethacin by prostaglandin El or E2. Mucosal application of aspirin had little effect on either ileum or colon but indomethacin caused some inhibition. 4 These results support the supposition that prostaglandins contribute to peristaltic activity.

Section: Introductionmentioning

confidence: 99%

Inhibition of Peristalsis in Guinea‐pig Isolated Ileum and Colon by Drugs That Block Prostaglandin Synthesis

Bennett¹,

Eley²,

Stockley³

1976

“…Studies employing inhibitors of prostaglandin action or synthesis indicate that in isolated intestine, prostaglandins contribute to the regulation of muscle tone and rhythmic activity (Bennett & Posner, 1971;Eckenfels & Vane, 1972;Ferreira, Herman & Vane, 1972;1976;Botting & Salzmann, 1974;Willis, Davison & Ramwell, 1974;Bennett, Eley & Stockley, 1975a;Burleigh, 1977). In vivo, prostaglandin E2 may help control human cardiac sphincter tone (Dilawari, Newman, Poleo & Misiewicz, 1975).…”

Section: Introductionmentioning

confidence: 99%

The Contribution of Prostaglandins in the Muscle of Human Isolated Small Intestine to Neurogenic Responses

Bennett¹,

Stockley

1977

In strips cut parallel to the longitudinal or circular muscle, indomethacin (2‐10 μg/ml) usually lowered the tone, thus probably accounting for the reduction of nerve‐mediated relaxations to electrical field stimulation. In longitudinal muscle strips, indomethacin enhanced contractions which occurred during electrical stimulation, probably because tone fell, but antagonized after‐contractions. By contrast, in the circular muscle indomethacin reduced initial contractions but enhanced after‐contractions. Prostaglandin E2 counteracted all of the effects of indomethacin in the longitudinal muscle and most of those in the circular muscle; prostaglandin F2α restored circular muscle tone. The results suggest that prostaglandins affect the muscle directly and contribute to the regulation of tone. They may also mediate non‐cholinergic contraction in longitudinal muscle and suppress contractility in the circular muscle.

“…Since PGE2-like material is released from the myenteric plexus during coaxial stimulation of the guinea-pig isolated ileum (Coceani et al, 1967;Botting & Salzmann, 1974), it may be argued that the action of cyclooxygenase inhibitors on ACh release is due to removal of a prostaglandin which normally amplifies ACh release. Thus if a prostaglandin plays a role at all in the ACh release process, that role would be facilitatory.…”

Section: Discussionmentioning

confidence: 99%

Cyclo‐oxygenase inhibitors antagonize indirectly evoked contractions of the guinea‐pig isolated ileum by inhibiting acetylcholine release

Okpako¹,

Taiwo²

1984

1The effects of indomethacin, sodium meclofenamate and ketoprofen on the contractile responses of the guinea-pig isolated ileum to directly and indirectly evoked stimuli were investigated. The effects of the cyclo-oxygenase inhibitors on acetylcholine (ACh) release from plexus containing longitudinal muscle strips were also studied. 2 The cyclo-oxygenase inhibitors reduced contractile responses to transmural stimulation (TMS) and nicotine at concentrations which had no effect on ACh-induced contractions.3 In whole ileum preparations (WIP) indomethacin and ketoprofen (40jig ml-') reduced TMS responses by 17 ± 1.8% and 12 ± 1.8% (n = 6), respectively (30 min incubation). In longitudinal muscle strips (LMS) in which Auerbach's plexus is exposed, indomethacin and ketoprofen (1 ig ml-1) reduced TMS responses by 28±2.3% and 34±2.7% (n =6), respectively (10 min incubation). Thus the cyclo-oxygenase inhibitors were up to 80 times more effective in LMS than in WIP. The drugs were similarly more effective in blocking nicotine contractions in LMS than in WIP. 4 The cyclo-oxygenase inhibitors reduced basal and stimulated ACh release from LMS. For example, indomethacin (1 ig ml'-) reduced stimulated ACh release by 35% after 10 min incubation. The percentage inhibition increased to 79% after 40 min incubation (n = 6). 5 Prostaglandin E2 (PGE2) (0.1-2.5 ng ml-') restored the contractile responses and ACh release depressed by the cyclo-oxygenase inhibitors but not the contractile responses depressed by atropine.PGF2. had no effect on mechanical responses or ACh release depressed by the cyclo-oxygenase inhibitors. 6 It is concluded that the cyclo-oxygenase inhibitors studied reduced responses to transmural stimulation and nicotine by inhibiting ACh release. The site of action is the postganglionic parasympathetic nerve. 7 It is suggested that the reason why previous investigators needed to use high doses of cyclooxygenase inhibitor in the ileum is because the action of the inhibitor is limited by diffusion barriers. There was no evidence to support the view that there is more than one pool of cyclo-oxygenase in guinea-pig gut.