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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.

Abstract：

:Rat cerebrocortical minislices were incubated with physiological saline in the absence or presence of 5 mM ammonium acetate ("ammonia") and/or inhibitors of osmosensitive amino acid transport: 50 microM niflumic acid and 100 microM N-ethyl-maleimide for 60 min, with medium changes after 20 min and 40 min. The efflux of endogenous taurine, glutamate and glutamine was assayed by high-performance liquid chromatography, and steady-state cell volumes were monitored in the slices with the [14C]inulin method. In the absence of ammonia, niflumic acid abolished taurine efflux but did not affect glutamate or glutamine efflux at all time-points, and increased cell volume at 20 min and 60 min. N-Ethyl-maleimide increased taurine, glutamine and glutamate efflux at 20 min and 40 min, inhibited taurine and glutamine efflux at 60 min, and increased cell volume at 20 min. Ammonia strongly stimulated taurine (by 380% at 20 min), and only moderately glutamate (30% at 20 min) or glutamine efflux (76% at 20 min). Ammonia increased cell volume above the control level at all time-points. Niflumic acid inhibited, but did not abolish ammonia-dependent taurine and glutamine efflux, and did not change glutamate efflux. The effects of ammonia + niflumic acid on cell volume did not differ from the effects of each compound separately. N-Ethyl-maleimide inhibited ammonia-dependent efflux of all three amino acids except for stimulation of glutamate efflux at 20 min. N-Ethyl-maleimide + ammonia decreased the cell volumes more than did each compound separately. It is concluded that although ammonia-induced taurine efflux is accompanied by an increase in cell volume, the underlying mechanism is not simply a cell volume regulatory response normally observed in hypoosmotic stress. Increased efflux of taurine, which is an inhibitory amino acid and a cell membrane protectant, may serve to counteract the deleterious effects of increased excitatory transmission accompanying acute hyperammonemic insult.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Zielińska M,Hilgier W,Law RO,Goryński P,Albrecht J

doi

10.1016/s0306-4522(98)00639-3

keywords:

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

631-8

issue

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(98)00639-3

journal_volume

pub_type

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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.