Acid In Mouse Brain Research Articles

Uptake of piperidine and pipecolic acid by synaptosomes from mouse brain

Piperidine is actively transported into the synaptosomal fraction of adult mouse brain. The transport mechanism appears to be Na+ independent but is temperature dependent and sensitive to ouabain. Analysis of kinetic experiments indicates only a "low-affinity" transport system to be present. By contrast the uptake of D,L-[(3)H]pipecolic acid at a concentration of 4 X 10(-7)M was temperature and Na+ dependent, ouabain sensitive, and revealed a two-component system with a Km = 3.9 plus or minus 0.17 X 10(-6)M, Vmax = 129 plus or minus 6 pmol/mg protein/3 min for the "high-affinity" system and a Km = 90.2 plus or minus 4.3 X 10 (-6)M, Vmax = 2.45 plus or minus 0.19 nmol/mg protein/3 min for the "low-affinity" system. Compounds structurally related to pipecolic acid such as glycine, L-proline, 4-amino-n-butyric acid, and 5-amino-n-valeric acid showed an inhibitory effect on uptake at a concentration of 10(-4)M. The demonstration of biosynthesis of pipecolic acid in mouse brain and the presence of a "high-affinity" sodium-dependent uptake system suggest a physiological role of this substance in the central nervous system.

Detection of thein vivo conversion of 2-pyrrolidinone to γ-aminobutyric acid in mouse brain

Labeled gamma-aminobutyric acid was detected in mouse brain following intravenous injections of deuterium labeled 2-pyrrolidinone. [2H6]Pyrrolidinone was prepared by the reduction of [2H4]succinimide with lithium aluminum deuteride. Quantification was accomplished by a gas chromatography mass spectrometry assay method. gamma-Aminobutyric acid and internal standard, 5-aminovaleric acid, were converted to volatile derivatives by treatment with N,N-dimethylformamide dimethyl acetal. Quantitative estimates were derived from peak area measurements obtained from monitoring the parent ions of the gamma-aminobutyric acid and internal standard derivatives by repetitive scanning during the GC run. The conversion of pyrrolidinone to gamma-aminobutyric acid may provide a method for labeling central gamma-aminobutyric acid pools.

Effect of pyridoxal administration on the contents of pyridoxal phosphate and gamma-aminobutyric acid in mouse brain.

Many mice treated with a high single dose of PL died in convulsions. The convulsions were very similar to those induced with some anti B6 in several ways: (1) a long latent period occurs betfore convulsions; (2) PLP levels in brain decrease; (3) GABA levels in brain, especially in synaptosomal fraction, decrease. The possibility that a deranged GABA metabolism in nerve ending may be a major cause of the convulsions is discussed.

Effect of convulsant and anticonvulsant agents on level and metabolism of ?-aminobutyric acid in mouse brain

1. The effect of the convulsant agents pentetrazole, picrotoxin, bicuculline, strychnine and isoniazid on the central level of gamma-aminobutyric acid (GABA) and the activity of the enzymes glutamate decarboxylase (GAD) and GABA-alpha-oxoglutarate aminotransferase (GABA-T) from mice brain was studied in vivo and vitro. In vivo, convulsant doses of picrotoxin and isoniazid lowered the level of GABA and the activity of GAD, whereas strychnine and bicuculline had no such effect. Pentetrazole inhibited GAD, but did not alter the GABA content. In vitro, all convulsants, except bicuculline, inhibited the activity of GAD; however, the concentrations of strychnine were far beyond the range that is reached in vivo by convulsant doses. Only isoniazid inhibited the activity of GABA-T in vivo as well as in vitro. 2. Phenobarbital, ethosuximide and trimethadione were about equally active in preventing convulsions induced by strychnine and picrotoxin, whereas diazepam was 9 times, and sodium valproate 3.5 times more active against convulsions elicited by picrotoxin. Phenytoin up to 100 mg/kg was ineffective against all chemoconvulsants. 3. Diazepam, sodium valproate, ethosuximide and trimethadione antagonized the inhibition of GAD and the decrease in GABA concentrations caused by isoniazid. Phenobarbital and phenytoin prevented the decrease of GABA but did not reverse the inhibition of GAD. 4. The results suggest a role played by the transmitter pool of GABA in the convulsant action of chemoconvulsants and in the anticonvulsant effect of antiepileptics clinically used in petit mal epilepsy.

The occurrence and metabolism In vitro of unesterified fatty acid in mouse brain

1. 1. A method has been developed for the isolation and estimation of unesterified fatty acid in tissue extracts. This is based on treatment of extracted lipid with diazomethane followed by isolation of the methyl esters by chromatography on a thin layer of alumina. 2. 2. It has been found that mouse brain contains appreciable quantities of unesterified fatty acid. 3. 3. The principal acids were palmitic, stearic, oleic and arachidonic acids. 4. 4. When mouse brain was incubated with sodium [I- 14C]acetate for periods up to 6 h, 28%–66% of the incorporation into lipid was into unesterified fatty acid. 5. 5. Of the principal acids acetate was incorporated into palmitic acid only.