Regulation of CSF composition--blocking chloride-bicarbonate exchange.
The possibility that the increase in cerebrospinal fluid (CSF) [HCO-3] observed during respiratory acidosis could be the result of a decrease in CSF [Cl-] was studied by blocking a putative Cl--HCO-3 exchange transport system. Anesthetized dogs (pentobarbital 30 mg, iv) were given either 4,4'-diisothiocyano-2,2'-disulfonate stilbene (DIDS, 0.02 mumol/kg) or pyridoxal 5-phosphate (P-5-P, 4 mumol/kg) in the lateral cerebral ventricles and maintained either normocapnic (RA) or hypercapnic (5% CO2). CSF and arterial Pco2, pH, [Na+], [K+], [Ca2+], [Cl-], and [lactate] were determined. [HCO-3] was calculated. Samples were drawn before and 4 h after the drug was administered. In control dogs on RA no significant change was observed in any measured parameter after 4 h. Dogs receiving either DIDS or P-5-P and on RA had decreased CSF [Na+] of 2-4 meq/l and CSF [Cl-] of 6 meq/l. CSF [HCO-3] in DIDS dogs decreased approximately 5 meq/l. There was no significant change in CSF [HCO-3] in P dogs. After 4 h of 5% CO2, control dogs had decreased CSF [Cl-] of 3 meq/l and CSF [HCO-3] increased approximately 4 meq/l. Dogs receiving DIDS or P-5-P and breathing 5% CO2 for 4 h had decreased CSF [Cl-] of 6-9 meq/l and [HCO-3] increased of 7-9 meq/l. CSF [Na+] did not change during respiratory acidosis in any group. It was concluded the Cl- transport in CSF can be interfered with by use of blocking agents which inhibit Cl--HCO-3 exchange channels.
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000136:Acid-Base Equilibrium; D000818:Animals; D001639:Bicarbonates / Q000134:cerebrospinal fluid*; D001812:Blood-Brain Barrier / Q000187:drug effects; D002712:Chlorides / Q000134:cerebrospinal fluid*; D004285:Dogs; D005260:Female; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000134:cerebrospinal fluid; D008297:Male; D011732:Pyridoxal Phosphate / Q000494:pharmacology
D001639:Bicarbonates; D002712:Chlorides; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D011732:Pyridoxal Phosphate; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid