Characterization of the GABA autoreceptor in human neocortex as a pharmacological subtype of the GABAB receptor.
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.
Fassio
A
A
Institute of Pharmacology and Pharmacognosy, University of Genoa, Italy.
Bonanno
G
G
Cavazzani
P
P
Raiteri
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D001596:Benzylamines / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D001932:Brain Neoplasms / Q000601:surgery; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D018755:GABA Agonists / Q000378:metabolism / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D006801:Humans; D008297:Male; D008875:Middle Aged; D009943:Organophosphorus Compounds / Q000378:metabolism / Q000494:pharmacology; D010721:Phosphinic Acids; D051381:Rats; D018080:Receptors, GABA-B / Q000378:metabolism
D001596:Benzylamines; D018755:GABA Agonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D010721:Phosphinic Acids; D018080:Receptors, GABA-B; C061388:3-aminopropylphosphinic acid; C052329:phaclofen; C083008:CGP 52432; C066430:CGP 35348; D001418:Baclofen