Anti-proliferative and anti-inflammatory actions of imidazoline agents - Are imidazoline receptors involved?

被引:48
作者
Regunathan, S [1 ]
Feinstein, DL [1 ]
Reis, DJ [1 ]
机构
[1] Cornell Univ, Coll Med, Div Neurobiol, Dept Neurol & Neurosci, New York, NY 10021 USA
来源
IMIDAZOLINE RECEPTORS AND THEIR ENDOGENOUS LIGANDS: CURRENT CONCEPTS AND THERAPEUTIC POTENTIAL | 1999年 / 881卷
关键词
D O I
10.1111/j.1749-6632.1999.tb09389.x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have shown, that cultured vascular smooth muscle cells (VSMC) and brain astroglial cells express I-receptors of the I-2 subtype. While imidazoline agents are anti-proliferative in smooth muscle cells, they increase the expression of glial fibrillary acidic protein (GFAP) in astrocytes. Because increases in GFAP suppress the induction of calcium-independent, inducible nitric oxide synthase (NOS-2), we measured whether idazoxan and related imidazolines and agmatine would also suppress the expression of NOS-2. Cultured astrocytes and macrophages, RAW 264.7 cell line, were incubated with lipopolysaccharide (LPS, 1 mu g/ml) or cytokine mixture in the presence of 1-100 mu M of idazoxan, agmatine, or other imidazoline agents. Idazoxan potently (IC50, 10 mu M) decreased the activity of NOS-2 in astrocytes, bur was less potent in RAW 264.7 cells. By contrast, agmatine was most potent in RAW 264.7 cells (IC50, 10 mu M) but less potent in glial cells and VSMC. Both idazoxan and agmatine decreased the activity of NOS-2 by reducing the levels of enzyme protein as measured by immunoblot and immunocytochemistry. No specific binding of [H-3]-idazoxan was observed in RAW 264.7 cell membranes. We-conclude that idazoxan, agmatine, and selected imidazoline agents inhibit the expression of NOS-2 and proliferation in primary glial cells and VSMC. While the antiproliferative actions appear mediated by I-receptors of the I-2 type, the anti-inflammatory response is probably not mediated by I-receptors but possibly by direct actions on signal transduction enzymes.
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收藏
页码:410 / 419
页数:10
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