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Hyponatremia is a highly morbid condition, present in a wide range of human pathologies, that exposes patients to encephalopathic complication and the risk of permanent brain damage and death. Treating hyponatremia has proved to be difficult and still awaits safe management, avoiding the morbid sequelae of demyelinizing and necrotic lesions associated with the use of hypertonic solutions. During acute and chronic hyponatremia in vivo, the brain extrudes the excessive water by decreasing its content of electrolytes and organic osmolytes. At the cellular level, a similar response occurs upon cell swelling. Among the organic osmolytes involved in both responses, free amino acids play a prominent role because of the large intracellular pools often found in nerve cells. An overview of the changes in brain amino acid content during hyponatremia in vivo is presented and the contribution of these changes to the adaptive cell responses involved in volume regulation discussed. Additionally, new data are provided concerning changes in amino acid levels in different regions of the central nervous system after chronic hyponatremia. Results favor the role of taurine, glutamine, glutamate, and aspartate as the main amino acid osmolytes involved in the brain adaptive response to hyponatremia in vivo. Deeper knowledge of the adaptive overall and cellular brain mechanisms activated during hyponatremia would lead to the design of safer therapies for the hyponatremic patient.

Newborn rats treated for the first weeks of life with guanidinoethane sulfonate (GES), a blocker of taurine transport producing taurine depletion, showed a severe disruption of photoreceptor structure. Photoreceptor damage consisted of a marked reduction of the size of the photoreceptor layer, deformation of the outer segments, and a profound disorganization of the disc membranes. The GES-induced degeneration pattern was very similar to that observed in cats fed a taurine-deficient diet. Injection of beta-alanine, another antagonist of taurine transport, also produced a disruption of photoreceptor structure. These results confirm the requirement of taurine for maintaining photoreceptor structure in different species.

The purpose of this study to assess the effect of the formula taurine/diltiazem/vitamin E on the progression of visual field loss in retinitis pigmentosa. A double blind, placebo controlled study in 62 patients: visual field threshold values were obtained in a Humphrey Field Analyzer from center (30 degrees) and periphery (30-60 degrees), every 4 months during 3-year follow-up. Data were analyzed by univariate regression, with slopes obtained from the best fit lines. Based on slope values, three groups of patients were identified as those showing negative, positive, or zero slope: > or = 1 to < or = +1. In controls (32 patients), at central area, the distribution in negative, zero, or positive slope was, respectively, 16 (50%), 11 (35%), and 5 (15%). In the treated group (30 patients) this distribution was 6 (20%) negative, 17 (53%) zero, and 7 (23%) positive slope. In periphery, 16 control patients were distributed as 11 (69%) negative, 4 (25%) zero, and 1 (6%) positive slope. In the treated group (17 patients), the distribution was opposite: 1 (6%) negative, 7 (41%) zero, and 9 (53%) positive slope. Nineteen patients receiving treatment up to 6 years showed similar distribution by slope values. Eight out of 9 patients switched from placebo (2 years) to treatment (2-3 years), showed improving changes in their slope values. A beneficial effect of the treatment decreasing the rate of visual field loss was observed, likely through a protective action from free radical reactions in affected photoreceptors.

Cultured cerebellar granule neurons exposed to gradual reductions in osmolarity (2 1.8 mOsm/min) maintained constant volume up to 2 50% external osmolarity (p o

The efflux of potassium (K(+)) and amino acids from hippocampal slices was measured after sudden exposure to 10% (270 mOsm), 25% (225 mOsm) or 50% (150 mOsm) hyposmotic solutions or after gradual decrease (-2.5 mOsm/min) in external osmolarity. In slices suddenly exposed to 50% hyposmotic solutions, swelling was followed by partial (74%) cell volume recovery, suggesting regulatory volume decrease (RVD). With gradual hyposmotic changes, no increase in cell water content was observed even when the solution at the end of the experiment was 50% hyposmotic, showing the occurrence of isovolumic regulation (IVR). The gradual decrease in osmolarity elicited the efflux of (3)H-taurine with a threshold at -5 mOsm and D-[(3)H]aspartate (as marker for glutamate) and at -20 mOsm for [(3)H]GABA. The efflux rate of [(3)H]taurine was always notably higher than those of [(3)H]GABA and D-[(3)H]aspartate, with a maximal increase over the isosmotic efflux of about 7-fold for [(3)H]taurine and 3- and 2-fold for [(3)H]GABA and D-[(3)H]aspartate, respectively. The amino acid content in slices exposed to 50% hyposmotic solutions (abrupt change) during 20 min decreased by 50. 6% and 62.6% (gradual change). Taurine and glutamate showed the largest decrease. An enhancement in (86)Rb efflux and a corresponding decrease in K(+) tissue content was seen in association with RVD but not with IVR. These results demonstrate the contribution of amino acids to IVR and indicate their involvement in this mechanism of cell volume control.

Isolated frog rod outer segments (ROS) incubated in a Krebs-bicarbonate medium, and illuminated for 2 h, show a profound alteration in their structure. This is characterized by distention of discs, vesiculation, and a marked swelling. The light-induced ROS disruption requires the presence of bicarbonate and sodium chloride. Replacement of bicarbonate by TRIS or HEPES protects ROS structure. Also, substitution of sodium chloride by sucrose or choline chloride maintains unaltered the ROS structure. Deletion of calcium, magnesium, or phosphate does not modify the effect produced by illumination. An increased accumulation of labeled bicarbonate and tritiated water is observed in illuminated ROS, as compared with controls in the dark. The presence of taurine, GABA, or glycine, at concentrations of 5-25 mM, effectively counteracts the light-induced ROS disruption. Taurine (25 mM) reduces labeled bicarbonate and tritiated water levels to those observed in the dark incubated ROS.

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