Type I and II metabotropic glutamate receptors mediate depressor and bradycardic actions in the nucleus of the solitary tract of anaesthetized rats

Abstract

The potential role of metabotropic glutamate (mGlu) receptors in cardiovascular function in the nucleus of the solitary tract was examined following the microinjection of a number of selective mGlu receptor compounds into this site of anaesthetized rats. The prototypic mGlu receptor selective agonist 1 S,3 R-1-amino-cyclopentane dicarboxylate elicited depressor and bradycardic actions following microinjection into the nucleus tractus solitarius, which were similar to those produced by l-glutamate. Similarly, decreases in blood pressure and heart rate were observed upon administration of the type I and II selective mGlu receptor agonists, ( R, S)-3,5-dihydroxyphenylglycine (DHPG) and 2 R,4 R-4-aminopyrrolidine-2,4-dicarboxylate (APDC), respectively. These actions of DHPG were selectively attenuated by (±)-1-aminoindane-1,5-dicarboxylate, a type I mGlu receptor antagonist, whilst cardiovascular responses to APDC were unaffected by this compound. Interestingly, the proposed type II antagonist, (2 S,4 S)-2-amino-4-(4,4-diphenylbut-1-yl)-pentane-1,5-doic acid, reduced the cardiovascular responses to intra-nucleus tractus solitarius administration of both APDC and DHPG. The type III mGlu receptor agonist, l-2-amino-4-phosphonobutyrate, however, failed to elicit any cardiovascular actions when microinjected into the nucleus tractus solitarius. These studies provide new evidence for functional type I and II mGlu receptors in modulating cardiovascular responses in the nucleus tractus solitarius.