The gamma-aminobutyric acid uptake inhibitor NO-711 potentiates 3-aminopropylphosphinic acid-induced actions in rat neocortical slices.
In rat neocortical slices maintained in Mg2+-free Krebs medium, the GABAB receptor agonists baclofen and 3-aminopropylphosphinic acid dose-dependently reduced the frequency of spontaneous discharges, 3-aminopropylphosphinic acid being 10 times less potent than baclofen. These were sensitive to the antagonist CGP 52432 (3-[[3,4-dichloro-phenyl)methyl]-amino]propyl](-P-diethoxymethyl)- phosphinic acid) (1, 5 and 10 microM). The GABA uptake inhibitor NO-711 (1-(2-(((diphenylmethylene)amino)oxy)ethyl)-1,2,5,6-tetrahydro-3-+ ++pyridinecarboxylic acid) (5 and 10 microM) produced 2.9 and 9 fold increases in the potency of 3-aminopropylphosphinic acid without affecting baclofen-induced responses. In this study, the low potency of 3-aminopropylphosphinic acid when compared to baclofen, may be attributed to its uptake by NO-711-sensitive GABA transporters.
Ong
J
J
Department of Anaesthesia and Intensive Care, The University of Adelaide, South Australia, Australia. jong@medicine.adelaide.edu.au
Kerr
D I
DI
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004594:Electrophysiology; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D019579:Neocortex / Q000187:drug effects* / Q000502:physiology; D009557:Nipecotic Acids / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010091:Oximes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018755:GABA Agonists; D018756:GABA Antagonists; D009557:Nipecotic Acids; D009943:Organophosphorus Compounds; D010091:Oximes; C061388:3-aminopropylphosphinic acid; C078793:NNC 711