RGD Reference Report - Relationships between glutamine, glutamate, and GABA in nerve endings under Pb-toxicity conditions. - Rat Genome Database

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Relationships between glutamine, glutamate, and GABA in nerve endings under Pb-toxicity conditions.

Authors: Struzynska, L  Sulkowski, G 
Citation: Struzynska L and Sulkowski G, J Inorg Biochem. 2004 Jun;98(6):951-8.
RGD ID: 1643208
Pubmed: PMID:15149801   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jinorgbio.2004.02.010   (Journal Full-text)

Glutamine (Gln), glutamate (Glu) and gamma-amino butyric acid (GABA) are essential amino acids for brain metabolism and function. Astrocytic-derived glutamine is the precursor of the two most important neurotransmitters: glutamate, an excitatory neurotransmitter, and GABA, an inhibitory neurotransmitter. In addition to their roles in neurotransmission these neurotransmitters act as alternative metabolic substrates that enable metabolic coupling between astrocytes and neurons. The relationships between Gln, Glu and GABA were studied under lead (Pb) toxicity conditions using synaptosomal fractions obtained from adult rat brains to investigate the cause of Pb neurotoxicity-induced seizures. We have found that diminished transport of [(14)C]GABA occurs after Pb treatment. Both uptake and depolarization-evoked release decrease by 40% and 30%, respectively, relative to controls. Lower expression of glutamate decarboxylase (GAD), the GABA synthesizing enzyme, is also observed. In contrast to impaired synaptosomal GABA function, the GABA transporter GAT-1 protein is overexpressed (possibly as a compensative mechanism). Furthermore, similar decreases in synaptosomal uptake of radioactive glutamine and glutamate are observed. However, the K(+)-evoked release of Glu increases by 20% over control values and the quantity of neuronal EAAC1 transporter for glutamate reaches remarkably higher levels after Pb treatment. In addition, Pb induces decreased activity of phosphate-activated glutaminase (PAG), which plays a role in glutamate metabolism. Most noteworthy is that the overexpression and reversed action of the EAAC1 transporter may be the cause of the elevated extracellular glutamate levels. In addition to the impairment of synaptosomal processes of glutamatergic and GABAergic transport, the results indicate perturbed relationships between Gln, Glu and GABA that may be the cause of altered neuronal-astrocytic interactions under conditions of Pb neurotoxicity.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Nervous System Lead Poisoning, Adult  ISOSlc6a1 (Rattus norvegicus)1643208; 1643208protein:increased expression:brain and synaptosomeRGD 
Nervous System Lead Poisoning, Adult  IEP 1643208protein:increased expression:brain and synaptosomeRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to lead ion  IEP 1643208 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc6a1  (solute carrier family 6 member 1)

Genes (Mus musculus)
Slc6a1  (solute carrier family 6 (neurotransmitter transporter, GABA), member 1)

Genes (Homo sapiens)
SLC6A1  (solute carrier family 6 member 1)


Additional Information