title: 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 1S,3R-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 2R,4R-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, (2S,4S)-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.
authors.affiliation: Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors.forename: N M
authors.initials: NM
authors.lastname: Jones
authors.forename: P M
authors.initials: PM
authors.lastname: Beart
authors.forename: J A
authors.initials: JA
authors.lastname: Monn
authors.forename: R E
authors.initials: RE
authors.lastname: Widdop
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001919:Bradycardia / Q000139:chemically induced; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D007189:Indans / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology*; D012118:Resorcinols / Q000494:pharmacology; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*
chemical_list: C095756:1-aminoindan-1,5-dicarboxylic acid; C097299:4-aminopyrrolidine-2,4-dicarboxylic acid; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D018698:Glutamic Acid; C079215:3,5-dihydroxyphenylglycine; D011392:Proline; D005998:Glycine