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Halothane‐Induced Alterations of Glucose and Pyruvate Metabolism in Rat Cerebra Synaptosomes
Author(s) -
Johnson G. V. W.,
Hartzell Charles R.
Publication year - 1985
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1985.tb07177.x
Subject(s) - halothane , acetylcholine , endocrinology , chemistry , medicine , metabolism , choline , metabolite , lactate dehydrogenase , nad+ kinase , biochemistry , glycolysis , biology , enzyme , organic chemistry
Synaptosomes isolated from rat cerebra were used to study the effects of the inhalational anesthetic, halothane, on cholinergic processes. To identify possible mechanisms responsible for the depression of acetylcholine synthesis, we examined the effects of halothane on precursor metabolite metabolism involved with supplying the cytosol with acetyl‐CoA for acetylcholine synthesis. Three percent halothane/air (vol/vol) depressed 14 CO 2 evolution from labeled pyruvate and glucose. Steadystate 14 CO 2 evolution from [1‐ 14 C]glucose was depressed 84% by halothane, while 14 CO 2 evolution from [6‐ 14 C]glucose and [3,4‐ 14 C]glucose was decreased 67 and 52%, respectively, when compared with control conditions. Halothane inhibited the activities of both pyruvate dehydrogenase (14% depression) and ATP‐citrate lyase (32% depression). Total synaptosomal acetyl‐CoA concentrations were unaffected by halothane. Three percent halothane/air (vol/vol) caused a 77% increase in medium glucose depletion rate from 1.38 nmol (mg protein) −1 min −1 to 2.44 nmol (mg protein) −1 min −1 . Production of lactate by the synaptosomes in the presence of halothane increased by 231% from a control rate of 1.44 nmol (mg protein) −1 min −1 to 4.77 nmol (mg protein) −1 min −1 . Lactate production rate from pyruvate was also enhanced by 56% in the presence of halothane. These data lend support to the concept that the NAD + /NADH potential may be involved in the halothane‐induced depression of acetylcholine synthesis.