3-aminopropylphosphinic-acid and Brain-Neoplasms

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.

Topics: Adolescent; Adult; Aged; Animals; Baclofen; Benzylamines; Binding, Competitive; Brain Neoplasms; Cerebral Cortex; Female; GABA Agonists; GABA Antagonists; GABA-A Receptor Antagonists; GABA-B Receptor Agonists; GABA-B Receptor Antagonists; Humans; Male; Middle Aged; Organophosphorus Compounds; Phosphinic Acids; Rats; Receptors, GABA-B