Involvement of aquaporin in thromboxane A2 receptor-mediated, G 12/13/RhoA/NHE-sensitive cell swelling in 1321N1 human astrocytoma cells.
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.
Saito
Masaki
M
Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Tanaka
Hiroyuki
H
Sasaki
Masako
M
Kurose
Hitoshi
H
Nakahata
Norimichi
N
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D051398:Aquaporin 1 / Q000378:metabolism; D051401:Aquaporin 4 / Q000378:metabolism; D020346:Aquaporins / Q000378:metabolism*; D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology; D003994:Bucladesine / Q000494:pharmacology; D049108:Cell Enlargement / Q000187:drug effects; D045744:Cell Line, Tumor; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism*; D006801:Humans; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000378:metabolism*; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
C496020:AQP1 protein, human; C496030:AQP4 protein, human; C109669:AQP9 protein, human; D051401:Aquaporin 4; D020346:Aquaporins; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D017923:Sodium-Hydrogen Exchangers; C066737:RHOA protein, human; D051398:Aquaporin 1; D003994:Bucladesine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020742:rhoA GTP-Binding Protein