Beschreibung:
<jats:p><i>Aims:</i> 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. <i>Methods:</i> 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. <i>Results:</i> Estradiol and progesterone, but not testosterone, hydrocortisone or cholesterol (each at 3–30 µ<i>M</i>), caused a prompt and concentration-related increase in the peristaltic pressure threshold at which propulsive muscle contractions were elicited. Mifepristone (RU-486; 30 µ<i>M</i>) did not prevent the inhibitory effect of progesterone, but blocked peristalsis per se. Pharmacological blockade of inhibitory neural pathways with N<sup>G</sup>-nitro-<i>L</i>-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 µ<i>M</i>), but not maximally (30 µ<i>M</i>), 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<sub>1</sub> receptor agonist GR-73,632. <i>Conclusion:</i> 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.</jats:p>