Drug modification of chloride transport in the choroid plexus- cerebrospinal fluid system of the rat

The mechanisms of anion and cation transport in the choroid plexus-cerebrospinal fluid (CP-CSF) system are a part of the blood-brain barrier system which provides a homeostatically regulated environment for the brain. The characteristics of CI transport in the CP-CSF system have been investigated both in vivo and in vitro. The following hypotheses have been tested in these studies: 1) that the primary carrier mechanism for CI transport in the CP is the CI-HCO3 antiport system which exists at both poles of the epithelial cell; and 2) that CI transport plays an important role in the CSF secretory process. The disulfonic stilbene (DIDS), a specific inhibitor of CI-HCO-3 exchange, was used to study the location and the mechanism of CI transport. Sprague-Dawley rats were used in all studies. Animals were nephrectomized under ether anesthesia and ketamine (80 mg/kg) was administered prior to placement of the animal in the stereotaxic instrument. Drugs were injected into the left lateral ventricle, and 36-Cl and 22-Na (100 microcuries/kg) were administered intraperitoneally (IP.) 30 min after drug treatment. The ventriculo-cistemal perfusion technique was used to measure the rate of formation of CSF during the control and drug treatment (DIDS and PGE2) periods. The quantity of 36-Cl and 22-Na in CSF, medulla and CPs was expressed as the percent of the tissue volume that would be occupied by the radioactivity if it existed at the same concentration as in the plasma water, i.e., Vd = 100 X (dpm/g tissue / dpm/g plasma H-2-O). Tissue electrolytes were extracted into a 0.02 N HNO-3-O.OI5 N Li solution and Na and K were measured by flame photometry. The results suggest that: 1) the CI-HCO-3 transport systems exist on both sides of the epithelial membrane of the CP; 2) DIDS inhibits CI and Na transport in the CP-CSF system; 3) as a result of inhibition of both CI and Na transport by DEDS, the rate of formation of CSF is decreased; and 4) PGE-2 stimulates the entry of CI into both CP and CSF which may account for its effect to increase the rate of formation of CSF. These observations support the hypothesis that CI transport may be one of the driving forces of CSF formation.