I.v. anaesthetic agents do not interact with the verapamil binding site on L-type voltage-sensitive Ca2+ channels.
In this study we have examined if the i.v. anaesthetic agents thiopentone, pentobarbitone, ketamine, etomidate, propofol and alphaxalone interact with the verapamil binding site on L-type voltage-sensitive Ca2+ channels in rat cerebrocortical membranes. Binding assays were performed in 1 ml volumes of Tris HCl 50 mmol litre-1, pH 7.4, for 90 min at 20 degrees C, with cerebrocortical membranes (200 micrograms of protein), the verapamil binding sites of which were radiolabelled with [3H]verapamil. Non-specific binding was defined in the presence of verapamil 10(-6) mol litre-1. The interaction of i.v. anaesthetics was determined by displacement of [3H]verapamil 0.2 nmol litre-1. The mean concentrations of anaesthetic producing 25% inhibition of specific binding (corrected for the competing mass of [3H]verapamil), K25, were (mmol litre-1): thiopentone 0.68 (SEM 0.14); pentobarbitone 1.22 (0.13); propofol 0.66 (0.10); etomidate 0.24 (0.03); alphaxalone 0.19 (0.02); and ketamine 0.75 (0.04). These concentrations exceeded those seen during anaesthesia and suggest that the neuronal verapamil binding site may not be an important target for i.v. anaesthetic agents.
Hirota
K
K
University Department of Anaesthesia, Leicester Royal Infirmary.
Lambert
D G
DG
D018686:Anesthetics, Intravenous / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002121:Calcium Channel Blockers / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D005260:Female; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000378:metabolism*
D018686:Anesthetics, Intravenous; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014700:Verapamil