The effect of metabolic acidosis and alkalosis on the H+-ATPase of rat cerebral microvessels.

To determine the role of the proton translocating adenosine triphosphatase (H+-ATPase) of the blood-brain barrier, the density of the 31 Kd subunit of the vacuolar type H+-ATPase was quantitated in isolated rat cerebral microvessels with immunoblotting techniques. To establish the tissue specificity of the findings, synaptosomal membranes were also studied. Metabolic acidosis was induced with 1.5% ammonium chloride in drinking water for five days. Metabolic alkalosis was induced with 2.35% NaHCO3 in drinking water and daily injections of 10 mg/Kg furosemide intraperitoneally for 5 days. The quantity of the 31 Kd subunit (in arbitrary units) in cerebral microvessels was significantly increased in acidosis (3.98 +/- 0.45) (p<0.05) and was significantly decreased in metabolic alkalosis (0.49 +/- 0.16) (p<0.00) compared to controls (1.77 +/- 0.73). In synaptosomal membranes, metabolic alkalosis was associated with significant decrease in the quantity of the 31 Kd subunit-H+-ATPase (0.62 +/- 0.12 vs 0.92 +/- 0.01) p<0.05. The increase in the 31 Kd subunit in synaptosomal membranes with acidosis did not reach statistical significance. It is concluded that the quantity of vacuolar H+-ATPase in the blood-brain barrier is modulated by blood H+ or HCO3- content. These changes may be relevant to the physiology of the acid-base balance in the central nervous system.