Modulation by prostaglandins of contractions in guinea-pig ileum

Bennett, A. B.; Eley, K. G.; Stockley, Helen L.

doi:10.1016/0090-6980(75)90142-2

Cited by 57 publications

(20 citation statements)

References 10 publications

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“…Inhibition by serosally applied aspirin was lost or reduced after addition of prostaglandin E2 (Bennett et al, 1975b) indicate that indomethacin at concentrations up to 3.6 jg/ml had no significant effect on contractions of the longitudinal muscle induced by ACh, and caused at most a small depression of contractions to electrical field stimulation at 4 Hz. However, indomethacin 20 jg/ml (Chong & Downing, 1974) or 40 gg/ml (Bennett et al, 1975b) caused non-selective depression.…”

Section: Drugsmentioning

confidence: 99%

“…However, indomethacin 20 jg/ml (Chong & Downing, 1974) or 40 gg/ml (Bennett et al, 1975b) caused non-selective depression. (Ambache et al, 1966).…”

Section: Drugsmentioning

confidence: 99%

“…These results suggest that prostaglandins may be involved in peristalsis. Furthermore, prostaglandin E may modulate the response to cholinergic nerve stimulation (Ehrenpreis, Greenberg & Belman, 1973;Chong & Downing, 1974;Kadlec, Masek & geferna, 1974;Bennett et al, 1975b). We therefore studied the effects of drugs which inhibit prostaglandin synthesis (Ferreira, Moncada & Vane, 1971;Smith & Willis, 1971;Vane, 1971) on peristaltic activity in guinea-pig isolated ileum and colon.…”

Section: Introductionmentioning

confidence: 99%

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

Bennett¹,

Eley²,

Stockley³

1976

British J Pharmacology

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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.

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Section: Drugsmentioning

confidence: 99%

“…However, indomethacin 20 jg/ml (Chong & Downing, 1974) or 40 gg/ml (Bennett et al, 1975b) caused non-selective depression. (Ambache et al, 1966).…”

Section: Drugsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Bennett¹,

Eley²,

Stockley³

1976

British J Pharmacology

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“…Diffusion related problems may thus explain why only high concentrations of inhibitor are effective in whole ileum preparations and the often observed long latent period in the action of these drugs (Ferreira et al, 1972; this study). Therefore, there is no evidence from this study to suppose that different pools of enzyme (extraneuronal and neuronal) exist with different sensitivities to blockade by cyclo-oxygenase inhibitors, as suggested by Bennett et al (1975b). It is tempting to speculate that, in therapeutic use, a greater diffusibility of cyclo-oxygenase inhibitors into inflamed areas, is the reason why these drugs exhibit fewer side effects than would be predicted from some important physiological roles attributed to the prostanoids (Hedqvist, 1974).…”

Section: Discussionmentioning

confidence: 73%

“…To explain the need for high concentrations of inhibitor, Bennett et al (1975b) proposed the existence of two pools of cyclo-oxygenase with different susceptibilities to blockade by indomethacin: an extraneuronal pool sensitive to low concentrations of indomethacin which mediates maintenance of muscle tone, and a cholinergic neuronal pool inhibited only by relatively high concentrations of indomethacin and which regulates transmitter release. An alternative view which is explored in these experiments is that the effectiveness of the inhibitors on 'neuronal' cyclo-oxygenase is limited by diffusion barriers.…”

Section: Introductionmentioning

confidence: 99%

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

Okpako¹,

Taiwo²

1984

British J Pharmacology

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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.

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Sphincteric function

Papasova

1989

Comprehensive Physiology

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Modulation by prostaglandins of contractions in guinea-pig ileum

Cited by 57 publications

References 10 publications

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

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

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

Sphincteric function

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