Differential effects of acetazolamide, benzolamide and systemic acidosis on hydrogen and bicarbonate gradients across the apical and basolateral membranes of the choroid plexus.
The effect after 1 hr of sulfonamide agents and systemic acidosis on pH (dimethyloxazolidinedione method) and [HCO3-] (calculated from pH and estimated cell pCO2) of choroid plexus epithelium was analyzed in adult Sprague-Dawley rats anesthetized with ether. Acetazolamide (20 mg/kg i.p.) caused a striking increase in choroid cell pH (7.0-7.45) and a substantial elevation in [HCO3-]i, and an alkalinization of cerebrospinal fluid (CSF); effects of benzolamide (3 mg/kg i.v.) were less marked. Acetazolamide-induced augmentation of steady-state pH was found in choroid plexus (0.45 pH unit) but not in submaxillary salivary gland, skeletal muscle, erythrocytes and cerebral cortex. Respiratory acidosis (blood pH 6.94) caused choroid cell pH to decrease less extensively than in the other tissues analyzed; metabolic acidosis (blood pH 7.23) did not significantly alter choroid plexus pH. Both sulfonamide agents and systemic acidoses significantly decreased the pH gradient between arterial blood and cisternal CSF. The sulfonamide-induced increase in choroid cell pH is attributed to suppression of buffering of OH- by CO2, leading to elevated [OH]i; and to a build-up in [HCO3-]i. Acetazolamide caused a reversal of the H+ and HCO3- gradients across the basolateral (plasma-facing) membrane of the choroid plexus. It is postulated that carbonic anhydrase inhibitors decrease CSF formation primarily by reducing Na+-H+ exchange at the basolateral membrane of the choroidal epithelium, and secondarily by slowing down HCO3- and Cl- exit across the CSF-facing membrane.
D000086:Acetazolamide / Q000494:pharmacology*; D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D001574:Benzolamide / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism*; D002245:Carbon Dioxide / Q000097:blood; D002540:Cerebral Cortex / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D002831:Choroid Plexus / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D006878:Hydroxides; D017665:Hydroxyl Radical; D011522:Protons; D051381:Rats; D011919:Rats, Inbred Strains; D013830:Thiadiazoles / Q000494:pharmacology*
D001639:Bicarbonates; D002712:Chlorides; D006878:Hydroxides; D011522:Protons; D013830:Thiadiazoles; D002245:Carbon Dioxide; D017665:Hydroxyl Radical; D001574:Benzolamide; D000086:Acetazolamide