Regulation of breathing, glycine, and other neurotransmitter amino acids in brain and cerebrospinal fluid during respiratory acidosis and ammonia infusion*

The ventilatory response and amino acid levels in dog brain and cerebrospinal fluid (CSF) were determined after one hour of respiratory acidosis at a narcotic level of 25–35% CO2, balance O2, that raised PaCO2 greater than 24 kPa, lowered pH of arterial blood to 6.66 ± 0.03 and pH of cisternal cerebrospinal fluid to 6.70 ± 0.03. Ventilation was 36 ± 4 liters/min (room air normal <5 liters/min). Cerebral brain tissue obtained by craniotomy was analyzed for amino acids by ion exchange liquid chromatography. Induced respiratory acidosis resulted in significant (P<.05) elevations of brain glycine, leucine, and lysine. Brain glutamate decreased and glutamine increased, but GABA did not significantly change. During hypercapnia, CSF leucine, lysine and serine significantly increased, and appeared to follow brain glycine levels. Intravenous ammonia infusion during hypercapnia did not alter brain NH3 or amino acid levels, but shifted the CO2 response to a point where ventilation decreased with increasing PaCO2. These results suggest that the neurotransmitters glycine and glutamate participate in physiological alterations that impair the ventilatory response during CO2 narcosis. In this study, ventilation was not depressed below room air control levels. However, the ventilatory response curve was greatly reduced in terms of the ratio ‘ventilation-per-kPa increase in partial pressure of carbon dioxide’ at PaCO2 24 kPa as compared to that normally observed at PaCO2 7 kPa.