Steroid control of uterine motility via gamma-aminobutyric acidA receptors in the rabbit: a novel mechanism?
gamma-Aminobutyric acid (GABA) is a regulator of uterine motility. Stimulation of GABAA receptors tonically inhibited contractions of rabbit uterine strips, while stimulation of GABAB receptors enhanced contractions. Steroids appeared to interact with GABAA receptors to modulate uterine contractility: tetrahydroprogesterone (THP) inhibited while pregnenolone sulphate (PS) increased contractions. THP rapidly antagonized the stimulatory effect of PS, but progesterone inhibited the contractions after a delay, suggesting that the known 'silencing' actions of progesterone on the uterus could be mediated via the metabolite THP, which potentiates the inhibitory function of GABAA receptors. This novel mechanisms may play a role in uterine function during pregnancy and parturition.
Majewska
M D
MD
Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland 21224.
Vaupel
D B
DB
D000818:Animals; D005260:Female; D011280:Pregnanolone / Q000494:pharmacology; D011284:Pregnenolone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology*; D011817:Rabbits; D011963:Receptors, GABA-A / Q000187:drug effects*; D013268:Stimulation, Chemical; D014590:Uterine Contraction / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011372:Progestins; D011963:Receptors, GABA-A; C018370:pregnenolone sulfate; D011374:Progesterone; D005680:gamma-Aminobutyric Acid; D011284:Pregnenolone; D011280:Pregnanolone