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.
Institute of Pharmacology and Pharmacognosy, University of Genoa, Italy.
A
A
Fassio
G
G
Bonanno
P
P
Cavazzani
M
M
Raiteri
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