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. 1973 Aug;134(4):1001–1008. doi: 10.1042/bj1341001

The acute action of ammonia on rat brain metabolism in vivo

Richard A Hawkins 1, Alexander L Miller 1, Richard C Nielsen 1, Richard L Veech 1
PMCID: PMC1177908  PMID: 4762748

Abstract

1. Acute NH4+ toxicity was studied by using a new apparatus that removes and freezes the brains of conscious rats within 1s. 2. Brains were removed and frozen 5min after intraperitoneal injection of ammonium acetate (2–3min before the onset of convulsions). Arterial [NH4+] rose from less than 0.01 to 1.74mm at 4–5min. The concentrations of all glycolytic intermediates measured, except glucose 6-phosphate, were increased by the indicated percentage above the control value as follows: glucose (by 41%), fructose 1,6-diphosphate (by 133%), dihydroxyacetone phosphate (by 164%), α-glycerophosphate (by 45%), phosphoenolpyruvate (by 67%) and pyruvate (by 26%). 4. Citrate and α-oxoglutarate concentrations were unchanged and that of malate was increased (by 17%). 5. Adenine nucleotides and Pi concentrations were unchanged but the concentration of creatine phosphate decreased slightly (by 6%). 6. Brain [NH4+] increased from 0.2 to 1.53mm. Net glutamine synthesis occurred at an average rate of 0.33μmol/min per g. 7. The rate of brain glucose utilization was measured in vivo as 0.62μmol/min per g in controls and 0.81μmol/min per g after NH4+ injection. 8. The arteriovenous difference of glucose and O2 increased by 35%. 9. No significant arteriovenous differences of glutamate or glutamine were detected. Thus, although much NH4+ was incorporated into glutamine the latter was not rapidly released from the brain to the circulation. 10. Plasma [K+] increased from 3.3 to 5.4mm. 11. The results indicate that NH4+ stimulates oxidative metabolism but does not interfere with brain energy balance. The increased rate of oxidative metabolism could not be accounted for only on the basis of glutamine synthesis. We suggest that increased extracellular [NH4+] and [K+] decreased the resting transmembrane potential and stimulated Na+,K+-stimulated adenosine triphosphatase activity thus accounting for the increased metabolic rate.

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Selected References

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