Okpako D T, Taiwo Y O
Br J Pharmacol. 1984 Jul;82(3):577-85. doi: 10.1111/j.1476-5381.1984.tb10796.x.
The 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. The cyclo-oxygenase inhibitors reduced contractile responses to transmural stimulation (TMS) and nicotine at concentrations which had no effect on ACh-induced contractions. In whole ileum preparations (WIP) indomethacin and ketoprofen (40 micrograms ml-1) 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 microgram 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. The cyclo-oxygenase inhibitors reduced basal and stimulated ACh release from LMS. For example, indomethacin (1 microgram ml-1) reduced stimulated ACh release by 35% after 10 min incubation. The percentage inhibition increased to 79% after 40 min incubation (n = 6). Prostaglandin E2 (PGE2) (0.1-2.5 ng ml-1) restored the contractile responses and ACh release depressed by the cyclo-oxygenase inhibitors but not the contractile responses depressed by atropine. PGF2 alpha 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.
研究了吲哚美辛、甲氯芬那酸钠和酮洛芬对豚鼠离体回肠对直接和间接诱发刺激的收缩反应的影响。还研究了环氧化酶抑制剂对含纵肌条丛中乙酰胆碱（ACh）释放的影响。环氧化酶抑制剂在对ACh诱导的收缩无影响的浓度下，降低了对透壁刺激（TMS）和尼古丁的收缩反应。在全回肠制剂（WIP）中，吲哚美辛和酮洛芬（40微克/毫升）分别使TMS反应降低了17±1.8%和12±1.8%（n = 6）（孵育30分钟）。在暴露有奥尔巴赫丛的纵肌条（LMS）中，吲哚美辛和酮洛芬（1微克/毫升）分别使TMS反应降低了28±2.3%和34±2.7%（n = 6）（孵育10分钟）。因此，环氧化酶抑制剂在LMS中的效力比在WIP中高80倍。这些药物在阻断LMS中尼古丁收缩方面也比在WIP中更有效。环氧化酶抑制剂降低了LMS中基础和刺激的ACh释放。例如，吲哚美辛（1微克/毫升）孵育10分钟后，刺激的ACh释放降低了35%。孵育40分钟后，抑制百分比增加到79%（n = 6）。前列腺素E2（PGE2）（0.1 - 2.5纳克/毫升）恢复了被环氧化酶抑制剂抑制的收缩反应和ACh释放，但没有恢复被阿托品抑制的收缩反应。前列腺素F2α对被环氧化酶抑制剂抑制的机械反应或ACh释放没有影响。6得出结论，所研究的环氧化酶抑制剂通过抑制ACh释放降低了对透壁刺激和尼古丁的反应。作用部位是节后副交感神经。7提示先前研究者在回肠中需要使用高剂量环氧化酶抑制剂的原因是抑制剂的作用受到扩散屏障的限制。没有证据支持豚鼠肠道中存在不止一种环氧化酶池的观点。
