Abstract |
The physiological role of the thromboxane A(2) (TXA(2)) receptor expressed on glial cells remains unclear. We previously reported that 1321N1 human astrocytoma cells pretreated with dibutyryl cyclic AMP ( dbcAMP) became swollen in response to U46619, a TXA(2) analogue. In the present study, we examined the detailed mechanisms of TXA(2) receptor-mediated cell swelling in 1321N1 cells. The cell swelling caused by U46619 was suppressed by expression of p115-RGS, an inhibitory peptide of G alpha(12/13) pathway and C3 toxin, an inhibitory protein for RhoA. The swelling was also inhibited by treatment with Y27632, a Rho kinase inhibitor and 5-(ethyl-N-isopropyl)amiloride ( EIPA), a Na(+)/H(+)-exchanger inhibitor. Furthermore, cell swelling was suppressed by the pretreatment with aquaporin inhibitors mercury chloride or phloretin in a concentration-dependent manner, suggesting that aquaporins are involved in U46619-induced 1321N1 cell swelling. In fact, U46619 caused [(3)H]H(2)O influx into the cells, which was inhibited by p115-RGS, C3 toxin, EIPA, mercury chloride and phloretin. This is the first report that the TXA(2) receptor mediates water influx through aquaporins in astrocytoma cells via TXA(2) receptor-mediated activation of G alpha(12/13), Rho A, Rho kinase and Na(+)/H(+)-exchanger.
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Authors | Masaki Saito, Hiroyuki Tanaka, Masako Sasaki, Hitoshi Kurose, Norimichi Nakahata |
Journal | Cellular signalling
(Cell Signal)
Vol. 22
Issue 1
Pg. 41-6
(Jan 2010)
ISSN: 1873-3913 [Electronic] England |
PMID | 19772916
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- AQP1 protein, human
- AQP4 protein, human
- AQP9 protein, human
- Aquaporin 4
- Aquaporins
- Receptors, Thromboxane A2, Prostaglandin H2
- Sodium-Hydrogen Exchangers
- RHOA protein, human
- Aquaporin 1
- Bucladesine
- 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
- GTP-Binding Protein alpha Subunits, G12-G13
- rhoA GTP-Binding Protein
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Topics |
- 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
(pharmacology)
- Aquaporin 1
(metabolism)
- Aquaporin 4
(metabolism)
- Aquaporins
(metabolism)
- Astrocytoma
(metabolism, pathology)
- Bucladesine
(pharmacology)
- Cell Enlargement
(drug effects)
- Cell Line, Tumor
- GTP-Binding Protein alpha Subunits, G12-G13
(metabolism)
- Humans
- Receptors, Thromboxane A2, Prostaglandin H2
(metabolism)
- Signal Transduction
- Sodium-Hydrogen Exchangers
(metabolism)
- rhoA GTP-Binding Protein
(metabolism)
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