3-Aminopropanephosphinic acid is a potent agonist at peripheral and central presynaptic GABAB receptors.
The actions of the GABA analog 3-aminopropanephosphinic acid (3-APA) were studied in the guinea-pig isolated ileal preparation and at synapses between cultured rat hippocampal neurons. Like the GABAB receptor agonist, baclofen, 3-APA inhibited the electrically evoked ileal twitch. The EC50 for 3-APA was 0.8 microM; the EC50 for baclofen was 9 microM. In addition, the depressant responses to 3-APA and baclofen were blocked by the GABAB receptor antagonists phaclofen, saclofen, 2-hydroxy-saclofen and delta-aminovaleric acid. 3-APA also mimicked the presynaptic action of baclofen at GABAergic synapses between embryonic rat hippocampal neurons in culture. 3-APA reduced the amplitude of inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) by greater than 50% at a concentration of 1 microM, while baclofen reduced synaptic transmission to a similar degree at 10 microM. 3-APA did not alter membrane conductance, nor did the drug alter postsynaptic responses to GABA. These data show that 3-APA is a potent agonist at presynaptic GABAB receptors in the periphery and on GABAergic neurons from the central nervous system. The activity of 3-APA at central postsynaptic GABAB receptors remains to be studied.
Ong
J
J
Department of Anaesthesia and Intensive Care, University of Adelaide, Australia.
Harrison
N L
NL
Hall
R G
RG
Barker
J L
JL
Johnston
G A
GA
Kerr
D I
DI
D000596:Amino Acids / Q000494:pharmacology; D021542:Amino Acids, Neutral; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects* / Q000196:embryology; D007082:Ileum / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010525:Peripheral Nerves / Q000187:drug effects*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects*
D000596:Amino Acids; D021542:Amino Acids, Neutral; D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; C061388:3-aminopropylphosphinic acid; C013809:5-aminovaleric acid; D001418:Baclofen