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1 Division of Neurosurgery, 3 Department of Pharmacology and Neuroscience, and 2 Neuropharmacology and Neuroscience Research Group, Albany Medical College, Albany, New York 12208
Volume-dependent anion channels permeable for
Cl
and amino acids are
thought to play an important role in the homeostasis of cell volume.
Astrocytes are the main cell type in the mammalian brain showing volume
perturbations under physiological and pathophysiological conditions. We
investigated the involvement of tyrosine phosphorylation in hyposmotic
medium-induced
[3H]taurine and
D-[3H]aspartate
release from primary astrocyte cultures. The tyrosine kinase inhibitors
tyrphostin 23 and tyrphostin A51 partially suppressed the
volume-dependent release of
[3H]taurine in a
dose-dependent manner with half-maximal effects at ~40 and 1 µM,
respectively. In contrast, the release of
D-[3H]aspartate
was not significantly affected by these agents in the same
concentration range. The inactive analog tyrphostin 1 had
no significant effect on the release of both amino acids. The data
obtained suggest the existence of at least two volume-dependent anion
channels permeable to amino acids in astrocyte cultures. One of these
channels is permeable to taurine and is under the control of tyrosine
kinase(s). The other is permeable to both taurine and aspartate, but
its volume-dependent regulation does not require tyrosine phosphorylation.
regulatory volume decrease; swelling-activated anion channels; excitatory amino acids; tyrosine phosphorylation; tyrphostins
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