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ENDOTHELIN-STIMULATED PROLIFERATION OF THORACIC ARTERY SMOOTH MUSCLE CELLS INVOLVES ACTIVATION OF MITOGEN-ACTIVATED PROTEIN KINASE

LI TIAN-CHANG，TONG LI-JIA, PANG YONG-ZHENG, LIU XIU-HUA, WANG XUE-QING, HU DA-YI, TANG CHAD-SHU

(Heart Center of Beijing Red Cross Chaoyang Hospital, Beijing 100020； Beijing Medical University, Institute of Cardiovascular Research, Beijing 100083)

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 BQ 12 3，but not by specific tyrosine kinase inhibitor Herbimycin A (Herb).Pre-
treatment with PKC activator PMA (phorbol myristate acetate) for 24 h (PKC downreg ulation)significantly attenuated ET-1一induced MAPK activation. These results indicate that:(1)ET- l-stimulated proliferation of VSMC involves the activation of MAPK and (2)ET-1-induced MAPK activation is mediated through ETA receptor and PKC.

Key words: Mitogen-activated protein kinase;Endothelin;;

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Citing This Article：

LI TIAN-CHANG，TONG LI-JIA, PANG YONG-ZHENG, LIU XIU-HUA, WANG XUE-QING, HU DA-YI, TANG CHAD-SHU. ENDOTHELIN-STIMULATED PROLIFERATION OF THORACIC ARTERY SMOOTH MUSCLE CELLS INVOLVES ACTIVATION OF MITOGEN-ACTIVATED PROTEIN KINASE. Acta Physiol Sin 1996; 48 (4): (in Chinese with English abstract).