Acetazolamide and insulin alter choroid plexus epithelial cell [Na+], pH, and volume.
Agents that inhibit or stimulate Na+ transport were tested for their effects on the ionic composition and volume of the in vivo choroid plexus (CP) epithelium. Ketamine-anesthetized adult Sprague-Dawley rats treated 1 h with acetazolamide or insulin were analyzed for choroid cell [Na+]i, [HCO3-]i, and pHi (dimethadione method); for transmembrane Na+ and H+ gradients; and for the kinetics of penetration of 22Na from plasma to plexus epithelium to CSF. Acetazolamide (25 mg/kg) reduced [Na+]i by 5-10 mmol/l and substantially elevated [HCO3-]i and pHi; the concurrent 22Na uptake by the in vivo choroid plexus and CSF, as quantified by the transfer coefficient, Kin (ml.g-1.h-1), was curtailed by 55-60%. Such effects on Na+ transport and distribution are likely secondary to the alkalinization of pHi induced by carbonic anhydrase inhibition. Conversely, insulin (3 U/kg ip) stimulated Na+ transport, i.e., manifested as enhanced uptake of 22Na from plasma to choroid cell and increased [Na+]i. For various treatments altering the basolateral membrane H+ gradient, the regression analysis of the 22Na Kin vs. log [H+]i/[H+]ISF (where ISF is interstitial fluid) was significant at P less than 0.01. This is consistent with effects mediated by Na(+)-H+ exchange. K+ and Cl- redistribution phenomena were coincident with altered Na+ transport, as choroidal cells retained K+, Cl-, and H2O after acetazolamide but lost K+, Cl-, and H2O with insulin treatment. A model is presented relating alterations in CP Na+ transport, KCl content, and cell volume. Overall, the findings encourage the postulate for effects of these drugs on Na+ transport basolaterally, either indirectly by attenuating [H+]i/[H+]ISF (acetazolamide) or directly by accelerating Na+ transport (insulin).
Johanson
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Department of Clinical Neurosciences, Brown University/Rhode Island Hospital, Providence 02902.
Murphy
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D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D002831:Choroid Plexus / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000494:pharmacology*; D007477:Ions; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D014867:Water / Q000378:metabolism
D007328:Insulin; D007477:Ions; D014867:Water; D006859:Hydrogen; D012964:Sodium; D000086:Acetazolamide