Rat retrotrapezoid nucleus iono- and metabotropic glutamate receptors and the control of breathing.
We injected 10 nl (unilateral) of glutamate receptor antagonists or agonists into the region of the retrotrapezoid nucleus and measured the phrenic nerve and blood pressure responses. The rats were chloralose-urethan anesthetized, paralyzed, vagotomized, and ventilated, and each injection location was verified anatomically. Integrated phrenic amplitude was most reliably affected. The N-methyl-D-aspartic acid (NMDA) antagonists 2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione (which affects both NMDA and non-NMDA receptors) both decreased baseline eucapnic phrenic amplitude and the CO2 response. Glutamate increased phrenic amplitude in a dose-dependent manner, an effect blocked by prior injection of the NMDA and non-NMDA antagonists at the same site. The response duration depended on the duration of the glutamate injection: responses to 3-s injections lasted a few minutes, and responses to 60-s injections lasted for > 30 min. The long-lasting effect was reproduced by injection of the metabotropic agonist 1(S),3(R)-aminocyclopentanedicarboxylic acid at 0.01-0.02 times the glutamate dose. We conclude that the rat retrotrapezoid nucleus has an endogenous source of glutamate that maintains eucapnic phrenic output and allows expression of the CO2 response. NMDA and possibly non-NMDA receptors are involved. Their stimulation increases phrenic output via ionotropic and metabotropic receptor processes with the latter resulting in long-lasting phrenic stimulation.
Nattie
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Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756.
Li
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D000758:Anesthesia; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D008526:Medulla Oblongata / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D010791:Phrenic Nerve / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015656:Respiratory Mechanics / Q000502:physiology*; D014628:Vagotomy
D018690:Excitatory Amino Acid Agonists; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid