Heinemann Akos, Pieber Doris, Holzer Peter
Department of Experimental and Clinical Pharmacology, Karl Franzens University, Graz, Austria.
Digestion. 2002;65(4):213-9. doi: 10.1159/000063820.
The effects of steroid hormones on propulsive peristalsis in the intestine were investigated in order to compare their adverse effect profile on this clinically most important motor pattern.
Peristalsis in isolated segments of the guinea pig small intestine was triggered by luminal distension and recorded via the peristalsis-associated changes of the intraluminal pressure. Drug effects on muscular activity were investigated in a circular muscle preparation of the ileum.
Estradiol and progesterone, but not testosterone, hydrocortisone or cholesterol (each at 3-30 microM), caused a prompt and concentration-related increase in the peristaltic pressure threshold at which propulsive muscle contractions were elicited. Mifepristone (RU-486; 30 microM) did not prevent the inhibitory effect of progesterone, but blocked peristalsis per se. Pharmacological blockade of inhibitory neural pathways with N(G)-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), naloxone (opioid receptor antagonist), apamin or suramin plus pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (P2 purinoceptor blockers) counteracted the inhibitory effect of submaximally (10 microM), but not maximally (30 microM), effective concentrations of progesterone. Estradiol and progesterone depressed circular muscle contractions evoked by cholecystokinin octapeptide to a larger degree than responses to the tachykinin NK(1) receptor agonist GR-73,632.
The peristaltic motor inhibition caused by sex steroids at micromolar concentrations arises primarily from a depressant action on intestinal muscle activity and may be particularly relevant for high-dose regimens of mifepristone.
研究甾体激素对肠道推进性蠕动的影响，以比较它们对这种临床上最重要的运动模式的不良反应特征。
通过肠腔扩张触发豚鼠小肠离体节段的蠕动，并通过肠腔内压力与蠕动相关的变化进行记录。在回肠环形肌制备物中研究药物对肌肉活动的影响。
雌二醇和孕酮，但不是睾酮、氢化可的松或胆固醇（均为3 - 30微摩尔），引起引发推进性肌肉收缩的蠕动压力阈值迅速且与浓度相关的增加。米非司酮（RU - 486；30微摩尔）不能预防孕酮的抑制作用，但本身会阻断蠕动。用N(G)-硝基-L-精氨酸甲酯（一氧化氮合酶抑制剂）、纳洛酮（阿片受体拮抗剂）、蜂毒明肽或苏拉明加磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸（P2嘌呤受体阻滞剂）对抑制性神经通路进行药理学阻断，可抵消亚最大（10微摩尔）但不是最大（30微摩尔）有效浓度孕酮的抑制作用。雌二醇和孕酮对胆囊收缩素八肽诱发的环形肌收缩的抑制程度大于对速激肽NK(1)受体激动剂GR - 73,632的反应。
微摩尔浓度的性类固醇引起的蠕动运动抑制主要源于对肠道肌肉活动的抑制作用，这可能与米非司酮的高剂量方案特别相关。
