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Lipopolysaccharide regulates both serotonin- and thrombin-induced intracellular calcium mobilization in rat C6 glioma cells: possible involvement of nitric oxide synthase-mediated pathway.
- Source :
-
Journal of neuroscience research [J Neurosci Res] 1998 Feb 15; Vol. 51 (4), pp. 517-25. - Publication Year :
- 1998
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Abstract
- To investigate the mechanisms by which lipopolysaccharide (LPS) affects Ca2+ signaling systems, we studied the effects of LPS on the serotonin (5-HT)- or thrombin-induced intracellular Ca2+ ([Ca2+]i) increase in rat C6 glioma cells. Pretreatment of the cells with 1 microg/ml LPS for 24 hr significantly inhibited [Ca2+]i increase induced by 10 microM 5-HT- or 0.5 U/ml thrombin. Its inhibitory effects were both dose- and time-dependent. Treatment with 1 mM dibutyryl cGMP (dbcGMP) for 30 min also significantly inhibited the 5-HT- and thrombin-induced [Ca2+]i increase to approximately 60-70% of control. However, simultaneous pretreatment with LPS and dbcGMP did not show any synergistic inhibition. The simultaneous pretreatment with LPS and the potent cGMP-dependent protein kinase (PKG) inhibitors H-8 and KT5823 for 24 hr significantly antagonized the inhibitory effect of LPS. Pretreatment of the cells with 1 microg/ml LPS for 24 hr significantly enhanced cGMP accumulation, while dexamethasone and NMMA (NOS inhibitors) significantly attenuated the LPS-induced enhancement in cGMP accumulation. In addition, pretreatment of the cells with 100 nM dexamethasone for 24 hr significantly suppressed LPS-induced inducible nitric oxide synthase (iNOS; type II NOS, NOS-II) protein expression. These results indicate that LPS may inhibit both 5-HT- and thrombin-induced [Ca2+]i increase via iNOS expression and PKG activation pathway in rat C6 glioma cells.
- Subjects :
- Animals
Calcium antagonists & inhibitors
Cyclic GMP analysis
Cyclic GMP antagonists & inhibitors
Cyclic GMP metabolism
Dexamethasone pharmacology
Dibutyryl Cyclic GMP pharmacology
Glioma
Intracellular Fluid physiology
Isoquinolines pharmacology
Nitric Oxide Synthase antagonists & inhibitors
Nitric Oxide Synthase biosynthesis
Nitric Oxide Synthase Type II
Nitroprusside pharmacology
Protein Kinase C antagonists & inhibitors
Rats
Tumor Cells, Cultured
Calcium metabolism
Lipopolysaccharides pharmacology
Nitric Oxide Synthase metabolism
Serotonin pharmacology
Signal Transduction drug effects
Thrombin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0360-4012
- Volume :
- 51
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of neuroscience research
- Publication Type :
- Academic Journal
- Accession number :
- 9514205
- Full Text :
- https://doi.org/10.1002/(SICI)1097-4547(19980215)51:4<517::AID-JNR11>3.0.CO;2-0