In vivo microdialysis reveals facilitatory metabotropic glutamate receptors regulating excitatory amino acid release in rat nucleus tractus solitarius

Abstract

The functional involvement of metabotropic glutamate receptors in nucleus tractus solitarius of the medulla has been examined by evaluating the action of the selective metabotropic glutamate receptor agonist trans-1-amino-cyclopentane-1,3-dicarboxylate on the extracellular release of L-glutamate and L-aspartate by in vivo microdialysis. Studies were performed in urethane anaesthetized rats, with a microdialysis probe being inserted into the medial nucleus tractus solitarius, which was constantly perfused with artificial cerebrospinal fluid (1 μ1/min). Following an equilibration period, samples were collected for amino acid analysis by HPLC. trans-1-Amino-cyclopentane-1,3-dicarboxylate produced 190% and 500% increases in basal release of L-glutamate and L-aspartate, respectively. trans-1-Amino-cyclopentane-1,3-dicarboxylate-evoked release of L-glutamate and L-aspartate was concentration-dependent (10–100 μM), and was calcium and tetrodotoxin-sensitive. Two metabotropic glutamate receptor antagonists, (+)-α-methyl-4-carboxyphenylglycine (200 μM) and (S)-4-carboxyphenylglycine (500 μM), when administered via a microdialysis probe, significantly attenuated the trans-1-amino-cyclopentane-1,3-dicarboxylate-evoked release of both L-glutamate and L-aspartate. Basal release was not altered by these two antagonists. Histological studies verified the location of the probe in the nucleus tractus solitarius. These studies provide the first evidence using in vivo microdialysis of functional metabotropic glutamate receptors, which seem to be facilitatory pre- and postsynaptically located receptors, in the rat nucleus tractus solitarius. On the basis of our findings, metabotropic glutamate receptors are likely to play key modulatory roles in regulating transmitter release.