R59949, a diacylglycerol kinase inhibitor, inhibits inducible nitric oxide production through decreasing transplasmalemmal L-arginine uptake in vascular smooth muscle cells
| Autor: | Ichiro Wakabayashi, Tomoyuki Nakano, Tomoko Shimomura, Kaoru Goto |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Diacylglycerol Kinase Vascular smooth muscle Interleukin-1beta Myocytes Smooth Muscle Nitric Oxide Synthase Type II Stimulation 030204 cardiovascular system & hematology Cycloheximide Arginine Nitric Oxide Muscle Smooth Vascular Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Piperidines Animals Enzyme Inhibitors Rats Wistar Protein kinase C Cells Cultured Diacylglycerol kinase Quinazolinones Pharmacology biology Dose-Response Relationship Drug Cell Membrane Biological Transport General Medicine Cell biology Nitric oxide synthase 030104 developmental biology chemistry Biochemistry biology.protein Intracellular |
| Zdroj: | Naunyn-Schmiedeberg's archives of pharmacology. 390(2) |
| ISSN: | 1432-1912 |
| Popis: | Although diacylglycerol kinase (DGK) is known to be expressed in vascular smooth muscle cell, its functional significance remains to be clarified. We hypothesized that DGK is involved in the pathway of cytokine-induced nitric oxide (NO) production in vascular smooth muscle cells. The purpose of this study was to investigate the effects of R59949, a diacylglycerol kinase inhibitor, on inducible nitric oxide production in vascular smooth muscle cell. Cultured rat aortic smooth muscle cells (RASMCs) were used to elucidate the effects of R59949 on basal and interleukin-1β (IL-1β)-induced NO production. The effects of R59949 on protein and mRNA expression of induced nitric oxide synthase (iNOS) and on transplasmalemmal l-arginine uptake were also evaluated using RASMCs. Treatment of RASMCs with R59949 (10 μM) inhibited IL-1β (10 ng/ml)-induced NO production but not basal NO production. Neither protein nor mRNA expression level of iNOS after stimulation with IL-1β was significantly affected by R59949. Estimated enzymatic activities of iNOS in RASMCs were comparable in the absence and presence of R59949. Stimulation of RASMCs with IL-1β caused a marked increase in transplasmalemmal l-arginine uptake into RASMCs. l-Arginine uptake in the presence of IL-1β was markedly inhibited by R59949, while basal l-arginine uptake was not significantly affected by R59949. Both IL-1β-induced NO production and l-arginine uptake were abolished in the presence of cycloheximide (1 μM). The results indicate that R59949 inhibits inducible NO production through decreasing transplasmalemmal l-arginine uptake. DGK is suggested to be involved in cytokine-stimulated l-arginine transport and regulate its intracellular concentration in vascular smooth muscle cell. |
| Databáze: | OpenAIRE |
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