title: Pharmacological characterisation of multiple components in the enhancement by pregnanolone and propofol of [3H]flunitrazepam binding to GABAA receptors.
abstract: The enhancement by pregnanolone (5 beta-pregnan-3 alpha-ol-20-one) and propofol (2,6-diisopropylphenol) of [3H]flunitrazepam (FNZ) binding to GABAA receptors in rat whole brain homogenate has been investigated. Two components in the concentration-effect relationship for pregnanolone were distinguished by the sensitivity of one component to antagonism by bicuculline and enhancement by muscimol, and the selective but weak antagonism of the bicuculline-insensitive component by 11-ketoprogesterone (4-pregnen-3,11,20-trione). Unlike pregnanolone, the enhancement by propofol of [3H]FNZ binding appeared to comprise a single component which was insensitive to 11-ketoprogesterone and was only slightly antagonised by bicuculline and slightly enhanced by muscimol. These results provide evidence for distinct GABA-dependent and GABA-independent components of the action of pregnanolone in the enhancement of [3H]FNZ binding, with the GABA-independent component being sensitive to 11-ketoprogesterone. The data also support the suggestion of different binding sites for pregnanolone and propofol.
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of London, U.K.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhong
authors.forename: M A
authors.initials: MA
authors.lastname: Simmonds
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D005445:Flunitrazepam / Q000378:metabolism*; D018755:GABA Agonists / Q000494:pharmacology; D018757:GABA Modulators / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology*; D011374:Progesterone / Q000031:analogs & derivatives / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism
chemical_list: D018686:Anesthetics, Intravenous; D018755:GABA Agonists; D018757:GABA Modulators; D011963:Receptors, GABA-A; D009118:Muscimol; D011374:Progesterone; D005445:Flunitrazepam; C016531:11-ketoprogesterone; D011280:Pregnanolone; D001640:Bicuculline; D015742:Propofol