Differences among effects of sedative-hypnotic drugs on GABA-mediated chloride flux: quench flow studies.
The effects of 40 microM pentobarbital (PB), 1 microM diazepam (DZ) and 50 mM ethanol (EtOH) on gamma-aminobutyric acid (GABA)-mediated chloride flux into rat cerebral cortical microsacs were studied during 50 ms incubations with 36Cl. A quench-flow machine was used, allowing for preincubations and incubation of precise duration. A 1 s preincubation with PB did not increase the already significant effect of PB on GABA-mediated flux during the 50 ms incubation, but the 1 s preincubation was necessary for showing the effect of diazepam. EtOH had no effect, whether or not it was added in the preincubation. When microsacs were preincubated with 32 microM GABA for 1 s, far greater potentiation of the GABA effect was seen when the PB was also present during the preincubation than when it was only introduced in the incubation. Preincubation with both DZ and GABA also had a greater effect than merely adding DZ into the incubation, after the preincubation with GABA. Ethanol had no effect when added either during or after the 1 s preincubation with GABA. The different effects of these sedatives on GABA-mediated chloride flux are strongly suggestive of different loci or mechanisms of action.
Department of Pharmacology, University of Toronto Ont., Canada.
S J
SJ
Mihic
P H
PH
Wu
H
H
Kalant
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D002712:Chlorides; D006993:Hypnotics and Sedatives; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D010424:Pentobarbital; D003975:Diazepam