Pregnenolone and its sulphate modulate GABAA-receptor-mediated contractile responses in the guinea-pig isolated ileum.
Pregnenolone and its sulphate had concentration-dependent dual actions on gamma-aminobutyric acid (GABAA)-receptor-mediated ileal contractile responses, enhancing at 0.001-1 microM but inhibiting at 10 microM. There was a sinistral shift of the GABA dose-response curve in the presence of 0.01 microM pregnenolone, with a significant potentiation over the lower concentration range of GABA (3-30 microM), whilst 10 microM pregnenolone depressed the curve by 50% without a significant change in the EC50, in a manner resembling non-competitive inhibition with picrotoxin. Pregnenolone and its sulphate evidently have modulatory actions at ileal GABAA-receptor complexes in keeping with those seen using neurochemical studies in the central nervous system.
Ong
J
J
Department of Pharmacology, University of Sydney, New South Wales, Australia.
Kerr
D I
DI
Johnston
G A
GA
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D011284:Pregnenolone / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000502:physiology*
D011963:Receptors, GABA-A; C018370:pregnenolone sulfate; D011284:Pregnenolone