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Caffeine Improves GABA Transport in the Striatum of Spontaneously Hypertensive Rats (SHR).
Neurotox Res
December 2021
Laboratório de Neurofarmacologia, Instituto Biomédico, Niterói, RJ, Brazil.
The spontaneously hypertensive rat (SHR) is an excellent animal model that mimics the behavioral and neurochemical phenotype of attention-deficit/hyperactivity disorder (ADHD). Here, we characterized the striatal GABA transport of SHR and investigated whether caffeine, a non-selective antagonist of adenosine receptors, could influence GABAergic circuitry. For this purpose, ex vivo striatal slices of SHR and Wistar (control strain) on the 35th postnatal day were dissected and incubated with [3H]-GABA to quantify the basal levels of uptake and release.
View Article and Find Full Text PDFNovel Functionalized Amino Acids as Inhibitors of GABA Transporters with Analgesic Activity.
ACS Chem Neurosci
August 2021
Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland.
Neuropathic pain resistance to pharmacotherapy has encouraged researchers to develop effective therapies for its treatment. γ-Aminobutyric acid (GABA) transporters 1 and 4 (mGAT1 and mGAT4) have been increasingly recognized as promising drug targets for neuropathic pain (NP) associated with imbalances in inhibitory neurotransmission. In this context, we designed and synthesized new functionalized amino acids as inhibitors of GABA uptake and assessed their activities toward all four mouse GAT subtypes (mGAT1-4).
View Article and Find Full Text PDFCharacterizing the transport and utilization of the neurotransmitter GABA in the bacterial pathogen Brucella abortus.
PLoS One
October 2020
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, United States of America.
The neurotransmitter gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the human brain; however, it is becoming more evident that this non-proteinogenic amino acid plays multiple physiological roles in biology. In the present study, the transport and function of GABA is studied in the highly infectious intracellular bacterium Brucella abortus. The data show that 3H-GABA is imported by B.
View Article and Find Full Text PDFEndoplasmic reticulum retention and degradation of a mutation in SLC6A1 associated with epilepsy and autism.
Mol Brain
May 2020
Department of Neurology, Vanderbilt University Medical Center, Nashville, USA.
Mutations in SLC6A1, encoding γ-aminobutyric acid (GABA) transporter 1 (GAT-1), have been recently associated with a spectrum of epilepsy syndromes, intellectual disability and autism in clinic. However, the pathophysiology of the gene mutations is far from clear. Here we report a novel SLC6A1 missense mutation in a patient with epilepsy and autism spectrum disorder and characterized the molecular defects of the mutant GAT-1, from transporter protein trafficking to GABA uptake function in heterologous cells and neurons.
View Article and Find Full Text PDFAirway Epithelial Cell Release of GABA is Regulated by Protein Kinase A.
Lung
June 2016
Department of Anesthesiology, Columbia University, 630 W 168th St., P&S Box 46, New York, NY, 10032, USA.
Introduction: γ-amino butyric acid (GABA) is not only the major inhibitory neurotransmitter in the central nervous system (CNS), but it also plays an important role in the lung, mediating airway smooth muscle relaxation and mucus production. As kinases such as protein kinase A (PKA) are known to regulate the release and reuptake of GABA in the CNS by GABA transporters, we hypothesized that β-agonists would affect GABA release from airway epithelial cells through activation of PKA.
Methods: C57/BL6 mice received a pretreatment of a β-agonist or vehicle (PBS), followed by methacholine or PBS.
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