Abstract
Release-regulating gamma-aminobutyric acidB (GABAB) autoreceptors were studied in synaptosomes from fresh specimens of human cerebral cortex. The K+ (12 mM)-evoked overflow of [3H]GABA was inhibited by the GABAB receptor agonists (-)-baclofen (EC50 = 1.48 microM) and 3-aminopropylphosphinic acid (3-APPA; EC50 = 0.034 microM). The effect of 10 microM (-)-baclofen was differentially reduced by the three GABAB receptor antagonists CGP 52432 ([3-[[(3,4-dichlorophenyl)methyl)amino]propyl]-(diethoxymethyl)- phosphinic acid), phaclofen and CGP 35348 (3-aminopropyl-(diethoxymethyl)- phosphinic acid). CGP 52432 was by far the most potent antagonist (IC50 = 0.09 microM). Phaclofen was about 700-fold less potent than CGP 52432 (IC50 = 70.0 microM) while CGP 35348 was ineffective up to 100 microM. The present results suggest that human and rat GABAB neocortical autoreceptors have similar pharmacological characteristics.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Animals
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Baclofen / analogs & derivatives
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Baclofen / metabolism
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Baclofen / pharmacology
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Benzylamines / metabolism
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Benzylamines / pharmacology
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Binding, Competitive
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Brain Neoplasms / surgery
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism*
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Female
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GABA Agonists / metabolism
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GABA Agonists / pharmacology*
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GABA Antagonists / pharmacology*
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GABA-A Receptor Antagonists
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GABA-B Receptor Agonists*
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GABA-B Receptor Antagonists
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Humans
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Male
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Middle Aged
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Organophosphorus Compounds / metabolism
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Organophosphorus Compounds / pharmacology
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Phosphinic Acids*
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Rats
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Receptors, GABA-B / metabolism
Substances
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Benzylamines
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GABA Agonists
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GABA Antagonists
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GABA-A Receptor Antagonists
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GABA-B Receptor Agonists
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GABA-B Receptor Antagonists
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Organophosphorus Compounds
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Phosphinic Acids
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Receptors, GABA-B
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3-aminopropylphosphinic acid
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phaclofen
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CGP 52432
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CGP 35348
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Baclofen