Binding of volatile anesthetics by proteins has been proposed as a mechanism of anesthesia. There is no evidence, however, that anesthetics at clinically relevant concentrations can interact directly with lipid - free preparations of receptors or signal transducing proteins. Calmodulin is a key regulator of metabolism in neurons and muscle cells. This study describes the effects of halothane on the binding of the neuropeptide vasoactive intestinal peptide (VIP) by calmodulin. It was found that : (1) Saturable complexation of (tyr1^0-125 1)VIP by calmodulin was absolutely Ca²⁺ -dependent, requiring mM metal concentrations for optimal binding. (2) Halothane produced a dose - dependent, biphasic inhibition of VIP - calmodulin complexation . Relatively low concentrations of halothane (0.15-0.27 mM) inhibited the complexation strongly up to 67% inhibition. (3) The inhibitory concentrations of halothane did not influence binding of VIP by monoclonal antibody.
It could be concluded that calmodulin may be the target molecule for halothane and that the mechanism of anesthesia by halothane involves direct interaction with cellular signal-transducing proteins .