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Actions of the general anesthetic propofol (2,6‐diisopropylphenol) on the binding of [ 3 h]nicotine to rat cortical membranes
Author(s) -
Prince Richard J.,
Lineberry Jeffrey W.,
Lippiello Patrick M.
Publication year - 1994
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430310204
Subject(s) - chemistry , propofol , acetylcholine receptor , dissociation constant , nicotine , nicotinic agonist , receptor , anesthetic , biophysics , membrane , dissociation rate , dissociation (chemistry) , reaction rate constant , acetylcholine , kinetics , anesthesia , pharmacology , biochemistry , medicine , biology , physics , quantum mechanics
[ 3 H]nicotine bound to rat cortical membranes in a biphasic manner consistent with previous models of receptor function. The kinetics of binding 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 constant 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 the 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‐dependent increase in the binding of [ 3 ]Hnicotine, which reached 147% of the control value at 3 mM propofol. The equilibrium binding of [ 3 H]nicotine was unaffected by the drug. These results are consistent with propofol causing enhanced desensitization at the cortical nicotinic acetylcholine receptor, suggesting an alternative to receptor agonists which bind to active sites as a method of modulating receptor function. © 1994 Wiley‐Liss, Inc.