title: [Endothelin-stimulated proliferation of thoracic artery smooth muscle cells involves activation of mitogen-activated protein kinase].
abstract: Endothelin (ET) is a potent vasoconstrictor whose responses are mediated through a common G-protein coupled receptor. So far little is known concerning its potential mitogenic capacity. In the present study, experiments were conducted to determine the role of mitogen-activated protein kinase (MAPK) activation in the rabbit thoracic artery smooth muscle cells (VSMC) in response to stimulation by ET-1. It was found that ET-1 produced concentration- and time-dependent increases in 3H-TdR incorporation and in MAPK activity of these cells. All the increases were inhibited by protein kinase C (PKC) inhibitors, such as Staurosporine (STP) and H-7 and by ETA receptor antagonist BQ123, but not by specific tyrosine kinase inhibitor Herbimycin A (Herb). Pre-treatment with PKC activator PMA (phorbol myristate acetate) for 24 h (PKC downregulation) significantly attenuated ET-1-induced MAPK activation. These results indicate that: (1) ET-1-stimulated proliferation of VSMC involves the activation of MAPK and (2) ET-1-induced MAPK activation is mediated through ETA receptor and PKC.
authors.affiliation: Heart Center of Beijing Red Cross Chaoyang Hospital.
authors.forename: T C
authors.initials: TC
authors.lastname: Li
authors.forename: L J
authors.initials: LJ
authors.lastname: Tong
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Pang
authors.forename: X H
authors.initials: XH
authors.lastname: Liu
authors.forename: X Q
authors.initials: XQ
authors.lastname: Wang
authors.forename: D Y
authors.initials: DY
authors.lastname: Hu
authors.forename: C S
authors.initials: CS
authors.lastname: Tang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D012692:Serial Passage
chemical_list: D019332:Endothelin-1; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases