Inhibition by female sex steroids of peristalsis in the guinea pig small intestine.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Heinemann
Akos
A
Department of Experimental and Clinical Pharmacology, Karl Franzens University, Graz, Austria. akos.heinemann@kfunigraz.ac.at
Pieber
Doris
D
Holzer
Peter
P
D000818:Animals; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D010528:Peristalsis / Q000187:drug effects* / Q000502:physiology; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology*; D012737:Sex Factors; D013256:Steroids / Q000494:pharmacology*
D012739:Gonadal Steroid Hormones; D013256:Steroids; D011374:Progesterone; D004958:Estradiol; D019001:Nitric Oxide Synthase