Halothane-induced alterations of cyclic nucleotide concentrations in three regions of the mouse nervous system.

Abstract

In an effort to determine whether halothane alters cyclic nucleotide levels in the nervous system, mice were exposed to air (control) or halothane 0.7, 1.4, 2.4, 3.0, or 4.4 per cent in air, for 15 minutes. After quick-freezing in liquid nitrogen, levels of 3,5‘-cyclic guanosine monophosphate (cGMP) and 3’,5‘-cyclic adenosine monophosphate (cAMP) in the cerebral cortex, cerebellum, and spinal cord were determined. Lactate and pyruvate were measured in the cerebral cortex and cerebellum as an index of brain oxygenation, and blood-gas and pH values were measured in replicate experiments. Three groups of studies were made: 1) control, 2) low halothane concentrations (0.7–2.4 per cent) without hypoxia and acidosis, and 3) high halothane concentrations (3.0 and 4.4 per cent) accompanied by hypoxia and acidosis. Low halothane concentrations increased cGMP in the cerebral cortex, depressed it in the cerebellum, and had no effect on levels in the spinal cord. Similar alterations were seen after exposure to high halothane concentrations that included a hypoxic component, except that cGMP in the spinal cord was depressed. Since anoxia decreases cGMP in the cerebral cortex and cerebellum, the increase in cGMP in the cortex suggests that the effect of halothane cannot be attributed to hypoxia. The only effect of halothane on cAMP was to depress the levels of the nucleotide in the cortex at halothane concentrations of 2.4 per cent or more. The authors conclude that halothane has a greater effect on cGMP than on cAMP, and that the biochemical responses to the anesthetic vary among regions of the nervous system.