Effect of carbonic anhydrase inhibitors and acidosis in choroid plexus epithelial cell sodium and potassium
Smith, Q.R.; Johanson, C.E.
Journal of Pharmacology and Experimental Therapeutics 215(3): 673-680
1980
ISSN/ISBN: 0022-3565 PMID: 7441525 Document Number: 156352
To elucidate the mechanism by which carbonic anhydrase inhibitors block fluid production by the choroid plexus (CP), Na-K transport by the rat choroidal epithelium was investigated by measuring acetazolamide- and benzolamide-induced changes in cell [K] and [Na]. Although plasma and CSF [K] and [Na] were not significantly altered after 1 h of drug treatment, acetazolamide (20 mg/kg) and benzolamide (40 mg/kg) decreased in vivo CP cell [Na] by 11-18 mmol/kg of cell H2O and substantially increased cell [K] by 25-35 mmol. Compensatory artificial respiration to control blood pH blocked the drug-induced effects of cell electrolytes. Acetazolamide (5 .times. 10-5 and 5 .times. 10-4 M) did not significantly alter cell [Na] or [K] in in vitro incubations of CP, although cell [K] tended to decrease in a drug concentration-dependent manner. Carbonic anhydrase inhibitors have no direct effect on the gradient for Na or K between choroid cell fluid and surrounding extracellular fluid. It is proposed that the carbonic anhydrase inhibitors reduced Na entry into the choroid epithelium across the basolateral membrane concurrent with a decrease in the rate of the apical membrane Na-K pump. To investigate whether the drug-induced extracellular acidosis changed cell electrolyte levels directly or indirectly, in vitro CP tissue incubations were performed in which the pH of the artificial CSF was varied from 7.24-7.44. CP cell [K] increased by 20 mmol/kg of H2O and cell [Na] fell by 10 when bathing medium pH was lowered from 7.39-7.24. Apparently the lowered blood pH directly stimulates K uptake and Na efflux from the CP cell, although an indirect effect of acidosis, either through an alteration of levels of circulatory hormones or of autonomic input to the CP, cannot be excluded.