title: Effects of inhibitors on chloride outflux from cerebrospinal fluid.
abstract: Movement of chloride from cerebrospinal fluid (CSF) to brain or blood is one of the factors that may be involved in regulation of CSF [Cl-], which is important to CSF acid-base balance. We made quantitative measurements of the unidirectional outflux of radiolabeled chloride (38Cl, half-life 37.3 min) from CSF in anesthetized dogs, using ventriculocisternal perfusion (VCP). The outflux of 38Cl from CSF was determined from the difference between the movements of 38Cl and dextran using a one-compartment model. VCP was performed at a rate of 1.4 ml/min for 14 min, and then slowed to 0.28 ml/min. The 38Cl activity decreased to a steady-state level approximately 12% lower than that of dextran within 40-50 min. Under control conditions for the first run (n = 24), the flux was 0.042 +/- 0.003 (SE) ml/min. The outflux under control conditions (n = 6) tended to increase over three separate determinations in a 6-h period, being 136 +/- 19% of the first run on the second run, and 143 +/- 24% on the third. There were no significant changes in 38Cl outflux compared with control ratios after the inclusion of bumetanide in the VCP fluid (n = 6), which inhibits sodium-coupled Cl- transport, with acetazolamide (n = 6), which inhibits carbonic anhydrase, or with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (n = 6), an inhibitor of carrier-mediated anion exchange. These results suggest that the outward movement of chloride from CSF occurs mostly by passive diffusion and is not by mediated transport.
authors.affiliation: Pulmonary Unit, Medical Services, Massachusetts General Hospital 02114.
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: D C
authors.initials: DC
authors.lastname: Johnson
authors.forename: H
authors.initials: H
authors.lastname: Kazemi
mesh_terms: D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology*; D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002034:Bumetanide / Q000494:pharmacology*; D002712:Chlorides / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D004232:Diuretics / Q000494:pharmacology*; D004285:Dogs; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D002712:Chlorides; D004232:Diuretics; D013267:Stilbenes; D002034:Bumetanide; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000086:Acetazolamide