Factors that affect the uptake of ammonia by the brain: the blood-brain pH gradient.

The brain uptake index (BUI) for [13N]ammonia was measured in 7 areas of the rat brain at 8 different pH values ranging from 6.58 to 7.73. When the regional BUI was plotted as a function of the pH of the test bolus, a significant linear correlation was found for each region (P less than 0.001). The highest slope was observed in the thalamus-basal ganglia complex (0.392 +/- 0.018) (S.D.), and the lowest in the ventral pons (0.143 +/- 0.011). These studies indicate that the brain-blood pH gradient plays a major role in determining the forward flux of ammonia from the blood into the brain in the physiological pH range. Regional differences in the slope may be due to metabolic factors. This pH effect may be important in clinical conditions characterized by hyperammonemia such as hepatic encephalopathy, and in the interpretation of [13N]ammonia emission tomographic images of the brain.