Thromboxane A2 receptor-mediated G12/13-dependent glial morphological change.
Glial cells express thromboxane A(2) receptor, but its physiological role remains unknown. The present study was performed to examine thromboxane A(2) receptor-mediated morphological change in 1321N1 human astrocytoma cells. Thromboxane A(2) receptor agonists U46619 and STA(2) caused a rapid morphological change to spindle shape from stellate form of the cells pretreated with dibutyryl cyclic AMP, but neither carbachol nor histamine caused the change, suggesting that G(q) pathway may not mainly contribute to the change. Rho kinase inhibitor Y-27632 inhibited U46619-induced morphological change, and U46619 increased the GTP-bound form of RhoA accompanied with actin stress fiber formation. These responses were reduced by expression of p115-RGS that inhibits G(12)/(13) signaling pathway. U46619 also caused the phosphorylation of extracellular signal-regulated kinase (ERK) and [(3)H]thymidine incorporation mainly through G(12)/(13)-Rho pathway. These results suggest that stimulation of thromboxane A(2) receptor causes the morphological change with proliferation mainly through G(12)/(13) activation in glial cells.
Honma
Shigeyoshi
S
Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Saika
Manami
M
Ohkubo
Satoko
S
Kurose
Hitoshi
H
Nakahata
Norimichi
N
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D001254:Astrocytoma / Q000473:pathology*; D003994:Bucladesine / Q000494:pharmacology; D045744:Cell Line, Tumor; D004247:DNA / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000502:physiology*; D006801:Humans; D010766:Phosphorylation; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology
D044244:Receptors, Thromboxane A2, Prostaglandin H2; D003994:Bucladesine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D004247:DNA; D048049:Extracellular Signal-Regulated MAP Kinases; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020742:rhoA GTP-Binding Protein