Possible Interaction: Alanine and Gamma-Aminobutyric Acid

“During treatment, an increase in the extracellular amino acids alanine , glycine, glutamate, aspartate, serine, threonine, and taurine was found demonstrating a significant influence on the intracellular pool of free amino acids induced by DAB.”

“The uptake of [3H]GABA was dependent on both extracellular Na+ and Cl– ions and was inhibited by (±)‐nipecotic acid, guvacine, and β‐alanine , with a pharmacological profile corresponding to that reported for the human homologue of the GABA/betaine transporter (BGT‐1).”

“This led serendipitously to the identification of a specific residue, alpha1F45, which, when mutated to an alanine , resulted in a significant decrease in potency for activation of the receptor by GABA and also reduced the efficacies of the partial agonists, THIP and P4S.”

“Furthermore, the uptake of [3H]GABA by MBEC4 cells was inhibited by GABA, taurine, β‐alanine and nipecotic acid in a concentration‐dependent manner.”

“This decrease probably occurred via inhibition of … GAT‐3 activity since their inhibitor, β‐alanine , induced … [3H]‐GABA uptake in punches of sham‐operated rats (−28%), but not in punches of 5,7‐DHT‐… that serotonin terminal degeneration had already impaired the β‐alanine‐sensitive component of GABA uptake.”

“Control autoradiography experiments showed that after short‐term exposure to radioactive amino acids, granule cells took up neither glutamate nor GABA, and β‐alanine predominantly inhibited astroglial GABA uptake.”

“The uptake of [3H]GABA in the presence of 1 mMβ‐alanine , which was employed to inhibit the glial uptake process, was reduced significantly in both the cerebral cortex and caudate‐putamen at the onset of neurological impairment (50‐62%) and at one subclinical stage (40‐51%).”

“1 The γ‐aminobutyric acid (GABA)‐induced contractile responses in the guinea‐pig isolated ileum, maintained in Krebs‐bicarbonate solution (pH 7.… of (±)‐cis‐3‐aminocyclohexane‐carboxylic acid (ACHC) > l‐2,4‐diaminobutyric acid (DABA) > (±)‐nipecotic acid > β‐alanine, whilst simultaneous addition of DABA … β‐alanine caused a … alone.”

“Turnover rates of the putative neurotransmitters (aspartate, glutamate, and GABA ) were 2–20‐fold higher than those of alanine and serine, and generally consistent with the proposed neurotransmitter functions for these amino acids.”

“1 Following preloading with [3H]‐γ‐aminobutyric acid [3H]‐GABA ), in the presence of β‐alanine to inhibit glial uptake of the label, electrical stimulation caused a frequency‐dependent release of tritium as [3H]‐GABA from isolated longitudinal‐muscle myenteric‐plexus preparations of the guinea‐pig ileum and colon.”