THE ACTIONS OF PHENYLGLYCINE DERIVED METABOTROPIC GLUTAMATE-RECEPTOR ANTAGONISTS ON MULTIPLE (1S,3R)-ACPD RESPONSES IN THE RAT NUCLEUS OF THE TRACTUS-SOLITARIUS

The effects of the metabotropic glutamate receptor (mGluR) agonist (1S ,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(IS,3R)-ACPD] and a se ries of phenylglycine-derived putative mGluR antagonists were examined on electrophysiological responses mediated by glutamate and GABA rece ptors in the nucleus of the tractus solitarius (NTS) in transverse bra insten slices of the rat. Monosynaptic excitatory currents (EPSC's) ev oked by electrical stimulation in the region of the tractus solitarius (TS) were reduced in the presence of (IS,3R)-ACPD in >90% of neurons recorded in the dorsomedial subdivision of the NTS adjacent to the are a postrema (AP). Monosynaptic evoked inhibitory currents (IPSC's) were similarly inhibited by (IS,3R)-ACPD. The inward current evoked by pre ssure application of pha-amino-3-hydroxy-5-methyl-4-isoxazole-propioni c acid (I-AMPA) was potentiated in the presence of (1S,3R)-ACPD, where as the outward current evoked by the gamma-amino-butyric acid-A (GABA- A) receptor agonist muscimol (I-MUSC) was inhibited. (1S,3R)-APCD also produced a postsynaptic inward current (I-K(ACPD)) associated with a decrease in membrane conductance in approximately 50%; of cells. The n ovel mGluR antagonists (S)-4-carboxy-3-hydroxy-phenylglycine (4C3H-PG) , (R,S)-4-carboxy-phenylglycine (4C-PG) and (R,S)-alpha-methyl-4-carbo xy-phenylglycine (alpha M4C-PG) reversibly antagonized the effects of (1S,3R)-ACPD on EPSC's IPSC's, I-AMPA and I-MUSC. The first two compou nds also displayed weak agonist activity. However, none of the antagon ists significantly inhibited I-K(ACPD) concentrations which blocked (1 S,SR)-ACPD effects on synaptic transmission. These results suggest tha t pharmacologically distinct mGluR's may be present in the NTS.