Taurine and osmoregulation. II. Administration of taurine analogues affords cerebral osmoprotection during chronic hypernatremic dehydration
H. Trachtman, R. Del Pizzo, J. A. Sturman, R. J. Huxtable and L. Finberg
Department of Pediatrics, Schneider Children's Hospital of Long Island Jewish Medical Center, NY.
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.