Aluminum and gallium arrest formation of cerebrospinal fluid by the mechanism of OH- depletion.
AlCl3 or GaCl3 was added to artificial cerebrospinal fluid and perfused through the cerebral ventricles of the rat. Depending on the metal and its concentration (1-10 mM) the pH of the perfusate ranged from 7.2 to 3.5. At 10 mM metal chloride, yielding pH 4.7 (Al) or 3.5 (Ga), formation of cerebrospinal fluid was suppressed 100%. The effect was reversed as soon as control cerebrospinal fluid (pH 7.35) was introduced. There was no effect at pH greater than 6 in the presence of metal ions nor was the effect mimicked by cerebrospinal fluid acidified with HCl or phosphate buffer to pH 4.7. HCl and phosphate at pH 4.7 had partial effects (25-30%). Inhibition of carbonic anhydrase is well known to have a partial effect (approximately 50%), the remainder of normal flow being dependent on the uncatalyzed formation of HCO3- and the corresponding movement of Na+. The complete cessation of flow after exposure to Al or Ga ions appears to occur when these ions are perfused at pH where they are partly hydrolyzed. Under these circumstances they form very powerful proton generating systems (as shown by titration data), which could lower [OH-] at the secretory border of choroid plexus cells. As a result, both the catalyzed and the uncatalyzed processes for formation of HCO3- from CO2 are abolished and secretion stops. This mechanism may also account for the antiperspirant action of Al salts. Using metal ion hydrolysis to probe other secretory systems will also be of interest.
Vogh
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Godman
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Maren
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D000086:Acetazolamide / Q000494:pharmacology; D000535:Aluminum / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D002555:Cerebrospinal Fluid / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005708:Gallium / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D051381:Rats
D006878:Hydroxides; D017665:Hydroxyl Radical; D005708:Gallium; D000535:Aluminum; D000086:Acetazolamide