Glutamate in the nucleus of the solitary tract activates both ionotropic and metabotropic glutamate receptors

Glutamate is the proposed neurotransmitter of baroreceptor afferents at the level of the nucleus of the solitary tract (NTS). Blockade of ionotropic glutamate receptors with kynurenic acid blocks the arterial baroreflex but, paradoxically, does not abolish the response to exogenous glutamate. This study tested the hypothesis that exogenous glutamate in the NTS activates both ionotropic and metabotropic glutamate receptors (mGluRs). In urethan-anesthetized rats, unilateral microinjections of glutamate into the NTS decreased mean arterial pressure, heart rate, and lumbar sympathetic nerve activity. The cardiovascular response to injection of glutamate was not altered by NTS blockade of mGluRs with alpha-methyl-4-carboxyphenylglycine (MCPG). Blockade of ionotropic glutamate receptors with kynurenic acid attenuated the response to glutamate injection. After combined NTS injection of MCPG and kynurenic acid, the response to glutamate was blocked. These data suggest that exogenous glutamate microinjected into the NTS acts at both ionotropic glutamate receptors and mGluRs. in addition, blockade of both classes of glutamate receptors is required to block the cardiovascular response to microinjection of glutamate in the NTS.