Subtypes of metabotropic glutamate receptors in the nucleus of the solitary tract of rats

Abstract

We have determined the role of subgroups of metabotropic glutamate receptors (mGluRs) in the nucleus of the solitary tract (NTS) of normotensive Wistar rats. Unilateral microinjection of ( S)-3,5-dihydroxyphenylglycine (3,5-DHPG), an agonist of group I mGluRs, into the NTS significantly decreased mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) (−19.4±2.6 mmHg, −16.4±5.1 beats/min, and −30.6±5.7% by 1 nmol). Microinjection of ( R, S)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 1 nmol), a putative antagonist of group I mGluRs, into the NTS caused transient decreases in MAP and RSNA, followed by sustained increases in MAP (+8.3±2.4 mmHg) and RSNA (+27.7±10.8%). Pretreatment with AIDA failed to prevent the cardiovascular and RSNA responses to microinjection of 3,5-DHPG. Unilateral microinjection of ( S)-4-carboxy-3-hydroxyphenylglycine (4C3HPG), an agonist of group II mGluRs, into the NTS also significantly decreased MAP, HR, and RSNA, whose responses were not inhibited by pre-microinjection of (2 S)-α-ethylglutamic acid (EGLU; 2 nmol), a putative antagonist of group II mGluRs. On the other hand, unilateral microinjection of l(+)-2-amino-4-phosphonobutyric acid ( l-AP4), an agonist of group III mGluRs, into the NTS caused dose-related decreases in MAP (−8.3±1.5 mmHg by 0.1 nmol and −45.1±3.4 mmHg by 0.3 nmol), HR, and RSNA (−21.3±3.9% by 0.1 nmol and −77.2±6.5% by 0.3 nmol), whose responses were suppressed by pre-microinjection of ( R, S)-α-cyclopropyl-4-phosphonophenylglycine (CPPG; 0.3 nmol), an antagonist of group III mGluRs. These results suggest that all subgroups of mGluRs participate in cardiovascular and sympathetic regulations in the NTS of rats, and that endogenous group I mGluRs in the NTS may contribute to tonic cardiovascular and sympathetic regulations.