ACTIONS OF THE GENERAL ANESTHETIC PROPOFOL (2,6-DIISOPROPYLPHENOL) ONTHE BINDING OF [H-3] NICOTINE TO RAT CORTICAL MEMBRANES

[H-3]nicotine bound to rat cortical membranes in a biphasic manner con sistent with previous models of receptor function. The kinetics of bin ding were characterized by a rapid component with a rate constant of 0 .007 min(-1) nM(-1) and a slower component with an apparent rate const ant of 0.024 min(-1). Dissociation was monophasic with a rate constant of 0.046 min(-1). Addition of 3 mM propofol caused the abolition of t he slow component of association and increased the rate constants for the rapid component to 0.012 min(-1) and for dissociation to 0.086 min (-1). Under non-equilibrium conditions propofol caused a dose-dependen t increase in the binding of [(3)Hnicotine, which reached 147% of the control value at 3 mM propofol. The equilibrium binding of [H-3]nicoti ne was unaffected by the drug. These results are consistent with propo fol causing enhanced desensitization at the cortical nicotinic acetylc holine receptor, suggesting an alternative to receptor agonists which bind to active sites as a method of modulating receptor function. (C) 1994 Wiley-Liss, Inc.