Evidence for a kynurenate-insensitive glutamate receptor in nucleus tractus solitarii.
Previous studies have shown that pharmacological blockade of ionotropic excitatory amino acid (EAA) receptors in the nucleus tractus solitarii (NTS) with kynurenate (Kyn) abolishes baroreceptor reflexes but fails to affect cardiovascular responses evoked by microinjections of L-glutamate (Glu) into the NTS. These observations have raised doubts as to whether Glu is a neurotransmitter of baroreceptor information in the NTS because the pharmacological actions of exogenously administered Glu are not identical to those of the neurotransmitter released in the NTS coincident with baroreceptor activation. One possible explanation for these results is that exogenously administered Glu might act at receptors that are not blocked by Kyn and are not accessible to synaptically released Glu in the NTS baroreflex pathway. The purpose of this study was to determine if Kyn-insensitive Glu receptors are present in the NTS. One candidate for this Kyn-insensitive receptor is the metabotropic EAA receptor that is selectively activated by trans-DL-1-amino-1,3-cyclopentane-dicarboxylic acid (ACPD). Microinjections of ACPD into the NTS of anesthetized rats produced dose-related depressor responses that were not reduced by Kyn or by pretreatment with the putative ACPD receptor antagonist L-2-amino-3-phosphonopropionate (L-AP-3). Similarly, depressor responses produced by Glu also were not affected by Kyn or by L-AP-3. These data demonstrate the presence of a Kyn-insensitive Glu receptor in the NTS. Moreover, they suggest that the failure of Kyn to reduce cardiovascular responses evoked by Glu injections into the NTS can be explained by an action of Glu at Kyn-insensitive ACPD receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Pawloski-Dahm
C
C
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322.
Gordon
F J
FJ
D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000294:innervation; D001794:Blood Pressure / Q000187:drug effects; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology*; D008526:Medulla Oblongata / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; C000211:2-amino-3-phosphonopropionic acid; D003515:Cycloleucine; D007051:Ibotenic Acid; C065594:cispentacin; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007736:Kynurenic Acid; D000409:Alanine