Metabotropic glutamate receptors in the ventrolateral medulla of rats.
We investigated the hypothesis that stimulation of metabotropic excitatory amino acid receptors in the ventrolateral medulla evokes cardiovascular responses. Thus, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD], a selective agonist of metabotropic excitatory amino acid receptors, was microinjected into the rostral or caudal ventrolateral medulla of halothane-anesthetized Sprague-Dawley rats. Microinjections of (1S,3R)-ACPD (100 pmol-1 nmol) into the rostral ventrolateral medulla produced dose-dependent increases in mean arterial pressure (+20 +/- 4 mm Hg by 100 pmol and +35 +/- 2 mm Hg by 1 nmol, p < 0.01 versus artificial cerebrospinal fluid) and integrated splanchnic sympathetic nerve activity (+17 +/- 3% and +46 +/- 4%, respectively, p < 0.01), whereas (1S,3+)-ACPD microinjected into the caudal ventrolateral medulla decreased mean arterial pressure (-28 +/- 2 mm Hg by 100 pmol and -48 +/- 6 mm Hg by 1 nmol, p < 0.01 versus artificial cerebrospinal fluid) and splanchnic sympathetic nerve activity (-24 +/- 4% and -49 +/- 5%, p < 0.01). The blockade of ionotropic excitatory amino acid receptors by the combined injection of 2-amino-7-phosphonoheptanoic acid (200 pmol) and 6,7-dinitroquinoxaline-2,3-dione (200 pmol), which effectively blocked the responses elicited by either N-methyl-D-aspartate (20 pmol) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (5 pmol), failed to affect the responses evoked by either (1S,3R)-ACPD (100 pmol) or L-glutamate (2 nmol) microinjected in the rostral and caudal ventrolateral medulla. These results suggest that metabotropic receptors are present and mediate cardiovascular responses evoked by L-glutamate injections into the rostral and caudal ventrolateral medulla.
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio.
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Averill
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism*; D013268:Stimulation, Chemical
D000596:Amino Acids; D004338:Drug Combinations; D011810:Quinoxalines; D017470:Receptors, Glutamate; C000211:2-amino-3-phosphonopropionic acid; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C056723:FG 9041; D015763:2-Amino-5-phosphonovalerate; D000409:Alanine; C031231:2-amino-7-phosphonoheptanoic acid