Propofol increases agonist efficacy at the GABA(A) receptor.
Using the whole-cell patch-clamp technique, we have determined that propofol, but not midazolam, increases the efficacy of piperidine-4-sulphonic acid (P4S), a partial agonist at alpha1beta1gamma2s, GABA(A) receptors expressed in HEK 293 cells. These findings are consistent with the idea that propofol facilitates receptor gating, while midazolam increases receptor occupancy by the agonist.
O'Shea
S M
SM
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637, USA.
Wong
L C
LC
Harrison
N L
NL
D000494:Allosteric Regulation; D018686:Anesthetics, Intravenous / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D004357:Drug Synergism; D018755:GABA Agonists / Q000737:chemistry / Q000494:pharmacology; D018757:GABA Modulators / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D007668:Kidney / Q000166:cytology; D008024:Ligands; D008874:Midazolam / Q000737:chemistry / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology; D015742:Propofol / Q000737:chemistry / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000502:physiology*
D018686:Anesthetics, Intravenous; D018755:GABA Agonists; D018757:GABA Modulators; D008024:Ligands; D010880:Piperidines; D011963:Receptors, GABA-A; C023402:piperidine-4-sulfonic acid; D008874:Midazolam; D015742:Propofol