RT Journal Article SR Electronic T1 Agonist and Potentiation Actions of n-Octanol on γ-Aminobutyric Acid Type A Receptors JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1011 OP 1019 DO 10.1124/mol.55.6.1011 VO 55 IS 6 A1 Yasutaka Kurata A1 William Marszalec A1 Jay Z. Yeh A1 Toshio Narahashi YR 1999 UL http://molpharm.aspetjournals.org/content/55/6/1011.abstract AB The n-octanol effects on the γ-aminobutyric acid type A (GABAA) receptor were studied in human embryonic kidney 293 cells transfected with α1, β2, and γ2S subunit cDNAs. GABA-evoked currents had an EC50 of 13.3 ± 1.7 μM and a Hill coefficient (nH) of 1.4 ± 0.1. n-Octanol was also capable of evoking a small current with an EC50 of 1000 μM and an nH of 2. In addition, n-octanol modulated GABA-induced currents in a concentration-dependent manner. Coapplications of n-octanol increased peak currents evoked by 3 μM GABA with an EC50 of 190 μM and an nH of 1.8. The extent of potentiation decreased with increasing GABA concentrations and no potentiation was observed whenn-octanol was coapplied with 1000 μM GABA. One-minute preapplication of 1000 μM n-octanol slightly potentiated 3 μM GABA-induced current, whereas it suppressed 300 μM GABA-induced current to 16% of the control, suggesting that 84% of the receptors underwent desensitization. Two models were used to explain n-octanol agonistic and potentiating actions on the α1β2γ2S GABAA receptor: n-octanol binds to multiple sites to exert multiple actions, orn-octanol acts as a partial agonist to manifest these actions. The partial agonist model is unique because it is a simpler model to explain n-octanol actions on the GABAA receptor.