Thromboxane A2 receptor mediated activation of the mitogen activated protein kinase cascades in human uterine smooth muscle cells

作者: Sinead M Miggin , B.Therese Kinsella

DOI: 10.1016/S0167-4889(01)00103-3

关键词:

摘要: Both thromboxane (TX) A2 and 8-epi prostaglandin (PG) F2α have been reported to stimulate mitogenesis of vascular smooth muscle (SM) in a number species. However, TXA2 8-epiPGF2α mediated mitogenic signalling has not studied detail human SM. Thus, using the uterine ULTR cell line as model, we investigated receptor (TP) cultured SMCs. TP agonist U46619 elicited time concentration dependent activation extracellular signal regulated kinase (ERK)s c-Jun N-terminal (JNK)s cells. Whereas antagonist SQ29548 abolished signalling, it only partially inhibited ERK JNK induced activations were by protein (PK) C, PKA phosphoinositide 3-kinase inhibitors GF109203X, H-89 wortmannin, respectively, but unaffected pertussis toxin. In addition, cells involves transactivation epidermal growth factor (EGF) receptor. humans, signals through two distinct isoforms. investigating involvement isoforms both TPα TPβ independently directed embryonic kidney (HEK) 293 over-expressing individual contrast that which occurred cells, HEK providing further evidence may alternative receptors, addition TPs,

参考文章(52)
Christopher J. Marshall, Sally J. Leevers, [28] Mitogen-activated protein kinase activation by scrape loading of p2lras Methods in Enzymology. ,vol. 255, pp. 273- 279 ,(1995) , 10.1016/S0076-6879(95)55030-5
Rongan Zhang, Martin L. Ogletree, Suzanne Moreland, Characterization of thromboxane A2/prostaglandin endoperoxide receptors in aorta European Journal of Pharmacology. ,vol. 317, pp. 91- 96 ,(1996) , 10.1016/S0014-2999(96)00697-8
R M Nüsing, M Hirata, A Kakizuka, T Eki, K Ozawa, S Narumiya, Characterization and chromosomal mapping of the human thromboxane A2 receptor gene. Journal of Biological Chemistry. ,vol. 268, pp. 25253- 25259 ,(1993) , 10.1016/S0021-9258(19)74595-5
T A Morinelli, C J Allan, P V Halushka, K Higashiura, D T Kurtz, G P Meier, M Martin, T W Gettys, O Geoffroy, Characterization of the cloned HEL cell thromboxane A2 receptor: evidence that the affinity state can be altered by G alpha 13 and G alpha q. Journal of Pharmacology and Experimental Therapeutics. ,vol. 277, pp. 1132- 1139 ,(1996)
M. Faure, T.A. Voyno-Yasenetskaya, H.R. Bourne, cAMP and beta gamma subunits of heterotrimeric G proteins stimulate the mitogen-activated protein kinase pathway in COS-7 cells. Journal of Biological Chemistry. ,vol. 269, pp. 7851- 7854 ,(1994) , 10.1016/S0021-9258(17)37127-2
L J Collins, M Yukawa, J A Ware, S H McGrail, K C Kent, M K Raychowdhury, Alternative splicing produces a divergent cytoplasmic tail in the human endothelial thromboxane A2 receptor. Journal of Biological Chemistry. ,vol. 269, pp. 19256- 19261 ,(1994) , 10.1016/S0021-9258(17)32161-0
K Yin, Y T Yan, P V Halushka, P Y Wong, Antiaggregatory activity of 8-epi-prostaglandin F2 alpha and other F-series prostanoids and their binding to thromboxane A2/prostaglandin H2 receptors in human platelets. Journal of Pharmacology and Experimental Therapeutics. ,vol. 270, pp. 1192- 1196 ,(1994)
B. Therese Kinsella, Garret A. Fitzgerald, Daniel J. O’Mahony, The Human Thromboxane A2 Receptor α Isoform (TPα) Functionally Couples to the G Proteins Gq and G11 In Vivo and is Activated by the Isoprostane 8-epi Prostaglandin F2α Journal of Pharmacology and Experimental Therapeutics. ,vol. 281, pp. 957- 964 ,(1997)