title: Differential effects of insulin on choline acetyltransferase and glutamic acid decarboxylase activities in neuron-rich striatal cultures.
abstract: We studied the effects of insulin, nerve growth factor (NGF), and tetrodotoxin (TTX) on cellular metabolism and the activity of glutamic acid decarboxylase (GAD) and choline acetyltransferase (ChAT) in neuron-rich cultures prepared from embryonic day 15 rat striatum. Insulin (5 micrograms/ml) increased glucose utilization, protein synthesis, and GAD activity in cultures plated over a range of cell densities (2,800-8,400 cells/mm2). TTX reduced GAD activity; NGF had no effect on GAD activity. Insulin treatment reversibly reduced ChAT activity in cultures plated at densities of greater than 4,000 cells/mm2, and the extent of this reduction increased with increasing cell density. The number of acetylcholinesterase-positive neurons was not reduced by insulin, suggesting that insulin acts by down-regulating ChAT rather than by killing cholinergic neurons. Insulin-like growth factor-1 (IGF-1) reduced ChAT activity at concentrations 10-fold lower than insulin, suggesting that insulin's effect on ChAT may involve the IGF-1 receptor. NGF increased ChAT activity; TTX had no effect on ChAT activity. These results suggest that striatal cholinergic and GABAergic neurons are subject to differential trophic control.
authors.affiliation: Department of Physiology and Biophysics, University of Miami School of Medicine, Florida 33101.
authors.forename: B J
authors.initials: BJ
authors.lastname: Brass
authors.forename: D
authors.initials: D
authors.lastname: Nonner
authors.forename: J N
authors.initials: JN
authors.lastname: Barrett
mesh_terms: D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism* / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000378:metabolism* / Q000502:physiology; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D007328:Insulin; D009414:Nerve Growth Factors; D013779:Tetrodotoxin; D007334:Insulin-Like Growth Factor I; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase