Inhibition by propofol of [3H]-batrachotoxinin-A 20-alpha-benzoate binding to voltage-dependent sodium channels in rat cortical synaptosomes

British Journal of Pharmacology
L Ratnakumari, H C Hemmings

Abstract

1. Propofol (2,6 di-isopropylphenol), an intravenous general anaesthetic, blocks voltage-dependent Na+ channels (Na+ channels). In this study the interaction between propofol and Na+ channels was analysed by examining its effects on neurotoxin binding to various receptor sites of the Na+ channel in rat cerebrocortical synaptosomes. 2. Propofol (10-200 microM) exhibited concentration-dependent inhibition of equilibrium binding of [3H]-batrachotoxinin-A 20-alpha-benzoate ([3H]-BTX-B) to receptor site 2 of the Na+ channel (mean IC50 = 26 microM; 6.5 microM free). Scatchard analysis revealed that propofol significantly increased the KD without affecting the Bmax for [3H]-BTX-B binding. 3. Kinetic studies of [3H]-BTX-B binding in the presence of various concentrations (25-200 microM) of propofol showed no significant changes in the association rate of [3H]-BTX-B. However, propofol at 200 microM significantly increased the rate of dissociation of [3H]-BTX-B, consistent with an indirect allosteric competitive mechanism of inhibition. 4. [3H]-saxitoxin binding to receptor site 1 and [3H]-brevetoxin-3 binding to receptor site 5 of the Na+ channel were not inhibited by propofol (10-200 microM). 5. Propofol (10-100 microM) exhibited conce...Continue Reading

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Citations

Aug 9, 2002·European Journal of Pharmacology·Peggy JouvertJean Zwiller
Jun 11, 2009·British Journal of Anaesthesia·H C Hemmings
Jan 25, 2007·Basic & Clinical Pharmacology & Toxicology·Yin DuanRussell A Nicholson
Jun 9, 2005·Brain Research. Developmental Brain Research·Xuehua SunLin Xu
Aug 12, 1999·Anesthesiology·B Rehberg, D S Duch
May 14, 1998·Anesthesiology·L Ratnakumari, H C Hemmings
Feb 25, 2005·Molecular Pharmacology·Hugh C HemmingsTimothy A Ryan
Feb 29, 2020·Current Neuropharmacology·Xuechao HaoCheng Zhou

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