Taurine and osmoregulation. II. Administration of taurine analogues affords cerebral osmoprotection during chronic hypernatremic dehydration.

Abstract

We have previously shown that in the cat, taurine is an osmoprotective molecule that lessens mortality, neurological morbidity, and brain-cell dehydration during chronic hypernatremic dehydration. We examined the ability of two taurine analogues to afford cerebral osmoprotection in rats. Pretreatment with guanidinoethane sulfonate, a competitive antagonist for beta-amino acid transport, as a 1% drinking solution for ten days led to a significant reduction in brain-cell dehydration. Thus, total brain-cell water was higher in experimental vs control animals (544.3 +/- 36.8 vs 478.2 +/- 12.7 mL/100 g of fat-free dry solids [FFDS]) and the difference was almost exclusively derived from the intracellular water compartment (452.7 +/- 27.3 vs 371.4 +/- 7.7 mL/100 g of FFDS). Pretreatment with taltrimide, a lipophilic taurine derivative (intraperitoneal injection of 200 mg/kg for four days), led to similar results. Total brain-tissue water was significantly higher in experimental vs control rats (507.6 +/- 18.8 vs 363.2 +/- 9.5 mL/100 g of FFDS), with the difference primarily derived from the intracellular water space (372.8 +/- 18.1 vs 221.3 +/- 13.1 mL/100 g of FFDS). These results suggest that the cerebral response to chronic hypertonic stress includes accelerated transmembrane flux of osmoprotective solutes in addition to mobilization from sequestered intracellular storage sites in an attempt to increase the cytosolic pool of osmotically active molecules.