Article date: 1989/1/1
PubMed ID: 2536422
Journal name: The Journal of pharmacology and experimental therapeutics (ISSN: 0022-3565)
Several lines of evidence suggest that dietary choline intake influences the metabolism of membrane phospholipids with possible effects on GABAergic neurotransmission. Based on these findings, the present experiments determined whether chronic choline supplementation or deficiency alters GABAergic function at the level of the gamma-aminobutyric acid (GABA)/benzodiazepine-chloride channel complex. To accomplish this, mice were fed diets containing 0% (deficient), 0.2% (basal) or 2.0% (supplemented) choline chloride for 28 days, and behavior, ligand binding at several sites in the complex and chloride uptake were determined in various brain regions. For both rotarod ataxia and open-field activity, mice receiving choline supplementation had a decreased response to clonazepam compared to those receiving basal and deficient diets. Choline supplementation significantly increased the in vivo binding of [3H]Ro15-1788 to cortex and cerebellum by 19% and 24%, respectively, and in vitro studies in cortical membranes indicated a significant 36% increase in the maximal number of [3H]flunitrazepam binding sites without a change in affinity, as compared to basal controls. In contrast, [3H]Ro15-1788 binding in vivo in all brain regions from mice fed the deficient diet decreased significantly to 20 to 58% of control values. Dietary choline intake did not alter GABA levels in brain, the binding of [35S]t-butylbicyclophosphorothionate to the chloride channel or the coupling between GABA and either the t-butylbicyclophosphorothionate site or the benzodiazepine site. However, the function of the GABAA receptor, determined by muscimol-stimulated chloride uptake into cortical synaptoneurosomes, was increased significantly in tissue from the supplemented group as compared to both control and deficient groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Author List: Miller L G, Greenblatt D J, Roy R B, Lopez F, Wecker L
Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.
Substances mentioned in the article: Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Chloride Channels; Chlorides; Membrane Proteins; Receptors, GABA-A; Flumazenil; tert-butylbicyclophosphorothionate; Choline;
Mesh terms: Animals; Brain/drug effects; Bridged Bicyclo Compounds/metabolism; Bridged Bicyclo Compounds, Heterocyclic; Chloride Channels; Chlorides/physiology; Choline/administration & dosage; Diet; Flumazenil/metabolism; Male; Membrane Proteins/physiology; Mice; Motor Activity/drug effects; Receptors, GABA-A/drug effects;