The acute action of ammonia on rat brain metabolism in vivo.
The acute action of ammonia on rat brain metabolism in vivo.
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DOI：
10.1042/bj1341001
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发表时间：
1973-08
期刊：
影响因子：
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通讯作者：
R. Hawkins;A. Miller;R. C. Nielsen;R. Veech
中科院分区：
文献类型：
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作者：
R. Hawkins;A. Miller;R. C. Nielsen;R. Veech
1.用一种新的装置，在1 s内取出并冷冻清醒大鼠的脑，研究了NH（4）（+）的急性毒性。2.腹腔注射醋酸铵后5分钟（惊厥发作前2- 3分钟），取出脑并冷冻。动脉血[NH（4）（+）]由<0.01上升到1.74mm。除葡萄糖6-磷酸外，测量的所有糖酵解中间体的浓度均以高于对照值的指定百分比增加，如下所示：葡萄糖（41%）、果糖1，6-二磷酸（133%）、二羟丙酮磷酸（164%）、α-甘油磷酸（45%）、磷酸烯醇丙酮酸（67%）和丙酮酸（26%）。4.柠檬酸盐和α-酮戊二酸盐浓度不变，苹果酸盐浓度增加（17%）。5.腺嘌呤核苷酸和P（i）浓度不变，但磷酸肌酸浓度略有下降（6%）。6.脑[NH（4）（+）]从0.2增加到1.53mm。谷氨酰胺净合成的平均速率为0.33 μ mol/min/g。7.脑葡萄糖利用率在对照组为0.62 μ mol/min/g，注射NH（4）（+）后为0.81 μ mol/min/g。8.葡萄糖和O2的动静脉差值增加了35%。9.谷氨酸盐或谷氨酰胺的动静脉差异不显著。因此，尽管大量NH（4）（+）被掺入谷氨酰胺中，但后者不会迅速从大脑释放到循环中。10.血浆[K（+）]由3.3增加到5.4mm。11.结果表明，NH（4）（+）刺激氧化代谢，但不干扰大脑能量平衡。氧化代谢速率的增加不能仅根据谷氨酰胺合成来解释。我们认为细胞外[NH（4）（+）]和[K（+）]的增加降低了静息跨膜电位并刺激了Na（+）、K（+）刺激的腺苷三磷酸酶活性，从而解释了代谢率的增加。
1. Acute NH(4) (+) 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 [NH(4) (+)] 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%), alpha-glycerophosphate (by 45%), phosphoenolpyruvate (by 67%) and pyruvate (by 26%). 4. Citrate and alpha-oxoglutarate concentrations were unchanged and that of malate was increased (by 17%). 5. Adenine nucleotides and P(i) concentrations were unchanged but the concentration of creatine phosphate decreased slightly (by 6%). 6. Brain [NH(4) (+)] increased from 0.2 to 1.53mm. Net glutamine synthesis occurred at an average rate of 0.33mumol/min per g. 7. The rate of brain glucose utilization was measured in vivo as 0.62mumol/min per g in controls and 0.81mumol/min per g after NH(4) (+) injection. 8. The arteriovenous difference of glucose and O(2) increased by 35%. 9. No significant arteriovenous differences of glutamate or glutamine were detected. Thus, although much NH(4) (+) 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 NH(4) (+) 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 [NH(4) (+)] and [K(+)] decreased the resting transmembrane potential and stimulated Na(+),K(+)-stimulated adenosine triphosphatase activity thus accounting for the increased metabolic rate.