Halothane effects on metabolic processes in cholinergic synaptosomes prepared from rat cerebra

Synaptosomes are an excellent model system for examining metabolic processes that occur in nerve endings. In this study they were used to examine the effects of halothane, an inhalational anesthetic, on metabolic processes associated with the synthesis of the neurotransmitter, acetylcholine. They were also used to study possible mechanisms involved with supplying the cytosol with activated acetyl groups produced in the mitochondria. In synaptosomes, halothane reversibly inhibits acetylcholine synthesis, and inhibits choline uptake in a competitive-like manner. It also depresses 14CO2 evolution from labeled pyruvate, glucose and succinate, decreases the activity of ATP-citrate lyase and pyruvate dehydrogenase, and completely inhibits pentose phosphate pathway activity. Halothane also significantly enhances glucose utilization and lactate production. However, halothane has no effect on choline acetyltransferases activity or total synaptosomal acetyl CoA levels. These alterations of metabolic processes leads to the suggestion that the primary effect of halothane is to decrease the NAD+/NADH potential, possibly resulting from mitochondrial NADH-CoQ reductase inhibition. This in combination with halothane's inhibition of choline transport would reduce the availability of both choline and acetyl CoA, precursors required for acetylcholine synthesis