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

The potential role of metabotropic glutamate (mGlu) receptors in cardiovasc ular function in the nucleus of the solitary tract was examined following t he microinjection of a number of selective mGlu receptor compounds into thi s site of anaesthetized rats. The prototypic mGlu receptor selective agonis t 1S,3R-1-amino-cyclopentane dicarboxylate elicited depressor and bradycard ic actions following microinjection into the nucleus tractus solitarius, wh ich 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-dihydroxyphenylglycin e (DHPG) and 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (APDC), respectivel y. These actions of DHPG were selectively attenuated by (+/-)-1-aminoindane -1,5-dicarboxylate, a type I mGlu receptor antagonist, whilst cardiovascula r responses to APDC were unaffected by this compound. Interestingly, the pr oposed type II antagonist, (2S,4S)-2-amino-4-(4,4-diphenylbut-1-yl)-pentane -1,5-doic acid, reduced the cardiovascular responses to intra-nucleus tract us solitarius administration of both APDC and DHPG. The type III mGlu recep tor agonist, L-2-amino-4-phosphonobutyrate, however, failed to elicit any c ardiovascular actions when microinjected into the nucleus tractus solitariu s. These studies provide new evidence for functional type I and II mGlu rec eptors in modulating cardiovascular responses in the nucleus tractus solita rius. (C) 1999 Elsevier Science B.V. All rights reserved.