Effects of ammonia in vitro on endogenous taurine efflux and cell volume in rat cerebrocortical minislices: influence of inhibitors of volume-sensitive amino acid transport
Section snippets
Preparation of rat cerebral cortical minislices and efflux assay
Female Wistar rats (150–220 g body weight; bred in the Medical Research Centre) were used throughout. In essence, a previously described procedure was followed,20., 21., 49. with slight modifications. Rats were killed by cervical dislocation, and cerebral hemispheres were excised and placed in ice-cold aerated standard medium (SM) containing (mmol/l): NaCl 126, MgSO4 1.29, NaH2PO4 1.29, KCl 5, CaCl2 0.8, HEPES 15, d-glucose 10, NaOH 11.7, pH 7.4. As opposed to the original procedure, no measures
Efflux of amino acids
Figure 1 shows the fractional efflux of each amino acid as calculated after 20, 40 and 60 min of incubation. Incubation with physiological saline (“control”) resulted in a stable fractional efflux of taurine. The efflux of glutamate and glutamine was most intense during the first 20 min, and markedly decreased thereafter. Ammonia exerted a strong stimulatory effect on taurine efflux; the most efficient stimulation was noted during the first 20 min of incubation (a 381% increase above control). By
Discussion
Previous studies have shown that acute or chronic treatment with ammonia stimulates the efflux of newly loaded radiolabelled taurine from different types of glial cells in culture,2., 6., 7., 8., 52. and upon prolonged treatment may increase cell volume in these cells.28 The principal novel observations of the present study are that: (i) ammonia induces efflux of endogenous taurine from cerebral cortex minislices, a preparation in which brain tissue is relatively intact, thus in an experimental
Conclusions
Ammonia promotes excitotoxic nerve cell damage by a mechanism involving excessive interaction of glutamate with NMDA receptors,23 following increased glutamate accumulation in the extracellular space25., 48. (for a recent review see Ref. 1). Increased glutamate efflux from ammonia-treated cerebrocortical minislices (Fig. 4) is in keeping with the above mechanism. Ammonia also compromises natural protection against excitotoxic damage, by depressing the synthesis of an endogenous glutamate
Acknowledgements
The study was supported by a statutory grant of the Medical Research Centre, Polish Academy of Sciences, and by the University of Leicester Research Board. We thank Professor Janusz Sadowski for constructive comments on the manuscript.
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