Type I and II metabotropic glutamate receptors regulate the outflow of [ [formula omitted]] d-aspartate and [ [formula omitted]]γ-aminobutyric acid in rat solitary nucleus

Abstract

Metabotropic glutamate (mGlu) receptors modulating amino acid outflow were examined in a model system in order to further characterize the pharmacological nature of the mGlu receptors involved in viscerosensory processing in the nucleus tractus solitarii. The actions of a number of subtype-selective mGlu receptor agonists and antagonists were monitored on the K +-evoked outflow of [ 3 H ] d-aspartate and [ 14 C ]γ-aminobutyric acid (GABA) from superfused slices of rat nucleus tractus solitarii. (±)1 S,3 R-1-Amino-cyclopentane-1,3-dicarboxylate (10–300 μM), produced a concentration-dependent increase in outflow, which was attenuated by a number of phenylglycine antagonists. (2 S,3 S,4 S)-α-(Carboxycyclopropyl)-glycine (30–300 μM) had mixed effects on outflow. The type I-selective agonist ( RS)-3,5-dihydroxyphenylglycine (300 μM) also increased outflow and these effects were reversed by the type I antagonist ( RS)-1-aminoindan-1,5-dicarboxylate (100 μM). Activation of type II mGlu receptors with (2 R,4 R)-aminopyrrolidine-2,4-dicarboxylate (300 μM), however, decreased outflow, and this effect was antagonized by the type II antagonist LY307452 (200 μM). Interestingly, LY307452 (200 μM) alone, enhanced outflow of [ 3 H ] d-aspartate, but not [ 14 C ]GABA. Type III mGlu receptors may not be involved in outflow of [ 3 H ] d-aspartate and [ 14 C ]GABA in the nucleus tractus solitarii, as l-2-amino-4-phosphonobutyrate (30–300 μM) had no effect under the present experimental conditions. These in vitro studies provide new evidence for roles for Type I and II mGlu receptors in viscerosensory processing in nucleus tractus solitarii.