Mutual Inhibition Kinetic Analysis of γ-Aminobutyric Acid, Taurine, and β-Alanine High-Affinity Transport into Neurons and Astrocytes: Evidence for Similarity Between the Taurine and β-Alanine Carriers in Both Cell Types
Autor: | Roger Griffiths, Ian C. Allen, Arne Schousboe, Orla M. Larsson |
---|---|
Rok vydání: | 2006 |
Předmět: |
Taurine
Biology Binding Competitive Biochemistry Aminobutyric acid Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Non-competitive inhibition medicine Animals Cells Cultured gamma-Aminobutyric Acid Cerebral Cortex Neurons Alanine chemistry.chemical_classification Biological Transport Membrane transport Embryo Mammalian Amino acid Kinetics medicine.anatomical_structure nervous system chemistry Astrocytes beta-Alanine Neuron Carrier Proteins Astrocyte |
Zdroj: | Journal of Neurochemistry. 47:426-432 |
ISSN: | 0022-3042 |
DOI: | 10.1111/j.1471-4159.1986.tb04519.x |
Popis: | The transport kinetics of γ-aminobutyric acid (GABA), taurine, and β-alanine in addition to the mutual inhibition patterns of these compounds were investigated in cultures of neurons and astrocytes derived from mouse cerebral cortex. A high-affinity uptake system for each amino acid was demonstrated both in neurons (KmGABA= 24.9 ± 1.7 μM; KmTau= 20.0 ± 3.3 μM; Kmβ-Ala= 73.0 ± 3.6 μM) and astrocytes (KmGABA= 31.4 ± 2.9 μM, KmTau= 24.7 ± 1.3 μM; Kmβ-Ala= 70.8 ± 3.6 μM). The maximal uptake rates (Vmax) determined were such that, in neurons, VmaxGABA> Vmaxβ-Ala=VmaxTau, whereas in astrocytes, Vmaxβ-Ala > VmaxTau=VmaxGABA. Taurine was found to inhibit β-alanine uptake into neurons and astro cytes in a competitive manner, with Ki values of 217 μM in neurons and 24 μM in astrocytes. β-Alanine was shown to inhibit taurine uptake in neurons and astrocytes, also in a competitive manner, with Ki values of 72 μM in neurons and 71 μM in astrocytes. However, β-alanine was found to be a weak noncompetitive inhibitor of neuronal and astrocytic GABA uptake, whereas in reverse experiments, GABA displayed weak noncompetitive inhibition of neuronal and astrocytic uptake of β-alanine. Likewise, taurine was a weak noncompetitive inhibitor of GABA uptake in neurons and similarly, GABA was a weak noncompetitive inhibitor of taurine uptake into neurons. Taken together, the similarity between the results obtained for β-alanine and taurine uptake in addition to their competitive mode of mutual inhibition strongly suggest that these compounds share a common carrier in neurons and astrocytes and that neither amino acid in either cell type is transported appreciably, if at all, by the GABA carrier, and vice versa. |
Databáze: | OpenAIRE |
Externí odkaz: |