3-aminopropanephosphinic acid is a potent agonist at peripheral and central presynaptic GABAB receptors

Abstract 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 GABA B receptor agonist, baclofen, 3-APA inhibited the electrically evoked ileal twitch. The EC 50 for 3-APA was 0.8μM; the EC 50 for baclofen was 9 μM. In addition, the depressant responses to 3-APA and baclofen were blocked by the GABA B receptor antagonists phaclofen, saclofen, 2-hydroxy-saclofen and δ-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 μM, while baclofen reduced synaptic transmission to a similar degree at 10 μM. 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 GABA B receptors in the periphery and on GABAergic neurons from the central nervous system. The activity of 3-APA at central postsynaptic GABA B receptors remains to be studied.