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  • Title: Effect of carbonic anhydrase inhibitors and acidosis in choroid plexus epithelial cell sodium and potassium.
    Author: Smith QR, Johanson CE.
    Journal: J Pharmacol Exp Ther; 1980 Dec; 215(3):673-80. PubMed ID: 7441525.
    Abstract:
    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 cerebrospinal fluid [K] and [Na] were not significantly altered after 1 hr of drug treatment, both acetazolamide (20 mg/kg) and benzolamide (40 mg/kg) decreased in vivo CP cell [Na] by 11 to 18 mmol/kg of cell H2O and substantially increased cell [K] by 25 to 35 mmol. Compensatory artificial respiration to control blood pH blocked the drug-induced effects of cell electrolytes. Furthermore, acetazolamide (5 x 10(-5) and 5 x 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. Thus, 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 cerebrospinal fluid was varied from 7.24 to 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 to 7.24. We postulate that 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.
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