Effects of glyceollin I on vascular contraction in rat aorta.
The present study was undertaken to investigate the molecular mechanisms by which glyceollin I inhibits vascular contraction in rat aorta. Rat aortic rings were treated with either glyceollin I or vehicle when vascular contraction reached plateaus. We measured the activity of GTP-RhoA and Rho GTPase-activating protein (RhoGAP) and the phosphorylation level of the myosin light chain (MLC(20)), myosin phosphatase targeting subunit 1 (MYPT1), and PKC-potentiated inhibitory protein for heterotrimeric MLCP of 17 kDa (CPI17). Glyceollin I reduced vascular contraction whether endothelium is present or denuded. Glyceollin I reduced vascular contraction induced by NaF, U46619, phenylephrine, or PDBu. Blockers of K(+) channels did not affect the vasorelaxation induced by glyceollin I. Glyceollin I reduced activation of RhoA as well as phosphorylation level of MLC(20). Glyceollin I also reduced phosphorylation of MYPT1 and CPI17 induced by NaF but not PDBu. However, glyceollin I had no direct effect on RhoGAP activation in vitro. Glyceollin I reduced vascular contraction, at least in part, through inhibition of the RhoA/Rho-kinase signaling pathway.
Song
Min-Ji
MJ
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu, 700-422, Republic of Korea.
Baek
Inji
I
Jeon
Su Bun
SB
Seo
Minchul
M
Kim
Yong-Hoon
YH
Cui
Song
S
Jeong
Yeon-Shin
YS
Lee
In-Jung
IJ
Shin
Dong Hyun
DH
Hwang
Young Hyun
YH
Kim
In Kyeom
IK
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D036343:Pterocarpans / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors
D018994:Myosin Light Chains; D047428:Protein Kinase Inhibitors; D036343:Pterocarpans; C017343:glyceollin; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein