Abstract
Inducible nitric oxide synthase (iNOS) is a molecule of great interest, given the numerous biological activities of nitric oxide and the documented expression of iNOS in several CNS pathologies. There also appears to be species-dependent regulation of iNOS expression as well as CNS-specific regulation. In this study, we have examined cultures of cytokine-activated primary human astrocytes as a model system with which to study the mechanisms of iNOS regulation in human CNS. As one of the major functions of astrocytes is spatial buffering of K+ ion, we examined the effect of high extracellular KCl on astrocyte iNOS expression. The results demonstrate that KCl at 25-75 mM potently inhibits astrocyte nitrite production stimulated by interleukin-1 (IL-1)/interferon-γ (IFNγ). In addition, several potassium channel inhibitors such as CsCl, tetraethylammonium, and 4-aminopyridine as well as nigericin inhibited astrocyte iNOS expression induced by IL-1/IFNγ. These results demonstrate a novel role for astrocyte potassium channel activity in modulation of astrocyte function. They further suggest neural-specific mechanisms for glial iNOS regulation.
Original language | English (US) |
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Pages (from-to) | 1903-1912 |
Number of pages | 10 |
Journal | Journal of Neurochemistry |
Volume | 74 |
Issue number | 5 |
DOIs | |
State | Published - 2000 |
Keywords
- Brain
- Cytokine
- Hyperkalemia
- Inflammation
- Interleukin-1
- Osmolarity
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience