title: Amobarbital inhibits K(+)-stimulated glucose oxidation in cerebellar granule neurons by two mechanisms.
abstract: The study aimed at determining mechanism(s) by which amobarbital (amytal) suppresses glucose oxidation in cerebellar granule neurons in primary cultures, a glutamatergic preparation. When challenged with a depolarizing K(+) concentration (55 mM), the cells doubled their rate of glucose oxidation (production of 14CO(2) from U-[14C]glucose) and glycolysis (lactate accumulation). At normal K(+) concentration, amobarbital reduced 14CO(2) production with half-maximum effect at 0.5-1 mM; at 55 mM K(+), the inhibition was more potent, with more than half of the K(+)-induced stimulation abolished at 50 microM. Dixon plot analysis showed a single inhibitory mechanism at 5.4 mM K(+), but at 55 mM K(+), two kinetically different mechanisms could be distinguished. A more pronounced compensatory amobarbital-induced increase in glycolysis at 5.4 than at 55 mM K(+) suggested that amobarbital in addition to its inhibition of mitochondrial respiration inhibited K(+)-induced increase in energy demand, probably by its known suppression of stimulated glutamate release.
authors.affiliation: Hong Kong DNA Chips, Limited, Kowloon, Hong Kong, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.forename: Leif
authors.initials: L
authors.lastname: Hertz
mesh_terms: D000654:Amobarbital / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003864:Depression, Chemical; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006019:Glycolysis; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007700:Kinetics; D019344:Lactic Acid / Q000096:biosynthesis; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D010084:Oxidation-Reduction; D011188:Potassium / Q000494:pharmacology*
chemical_list: D006993:Hypnotics and Sedatives; D019344:Lactic Acid; D018698:Glutamic Acid; D000654:Amobarbital; D005947:Glucose; D011188:Potassium