Abstract
We examined modulation of [(3)H]GABA uptake in slices of the rat globus pallidus because stimulation of adenosine A(2A) receptors increases extracellular GABA in this structure. Pharmacological analysis showed that GAT-1 is the main transporter present in these slices. Both adenosine and the A(2A) agonist CGS 21680 reduced GABA uptake. Antagonist ZM 241385 prevented these effects. Agents that increase protein kinase A activity like forskolin and 8-bromo-cAMP also inhibited GABA uptake. The inhibition of uptake produced by these substances and by CGS 21680 was prevented by the protein kinase A blocker H-89. The protein phosphatase blocker okadaic acid reduced uptake; this effect and the response to CGS 21680 were not additive. The effective concentrations of adenosine (EC(50)=15.2microM) are within the range measured in the interstitial fluid under some physiological conditions. Thus, inhibition of uptake may be important in increasing interstitial GABA during endogenous adenosine release.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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8-Bromo Cyclic Adenosine Monophosphate / pharmacology
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Adenosine / analogs & derivatives
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Adenosine / metabolism
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Adenosine / pharmacology
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Adenosine A2 Receptor Agonists*
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Animals
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Colforsin / pharmacology
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Data Interpretation, Statistical
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Enzyme Inhibitors / pharmacology
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GABA Plasma Membrane Transport Proteins / physiology*
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Globus Pallidus / drug effects
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Globus Pallidus / metabolism*
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In Vitro Techniques
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Isoquinolines / pharmacology
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Male
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Okadaic Acid / pharmacology
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Phenethylamines / pharmacology
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Rats
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Rats, Wistar
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Sulfonamides / pharmacology
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Synapses / drug effects
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Synapses / metabolism
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Triazines / pharmacology
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Triazoles / pharmacology
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gamma-Aminobutyric Acid / metabolism*
Substances
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Adenosine A2 Receptor Agonists
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Enzyme Inhibitors
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GABA Plasma Membrane Transport Proteins
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Isoquinolines
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Phenethylamines
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Sulfonamides
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Triazines
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Triazoles
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ZM 241385
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2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
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Colforsin
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Okadaic Acid
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8-Bromo Cyclic Adenosine Monophosphate
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gamma-Aminobutyric Acid
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Cyclic AMP-Dependent Protein Kinases
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Adenosine
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N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide