Effects of gomisin A on vascular contraction in rat aortic rings.
Gomisin A (GA) is an active ingredient of the fruits of Schisandra chinensis which has been widely used as a tonic in traditional Korean medicine. GA induces not only endothelium-dependent but also endothelium-independent relaxation in an isolated rat's thoracic aorta. This study was aimed to investigate the molecular mechanism by which GA induces endothelium-independent vasorelaxation. Rat aortic rings were denuded of endothelium, mounted in organ baths, and subjected to contraction or relaxation. We measured the amount of GTP RhoA as well as the phosphorylation level of 20 kDa myosin light chains (MLC₂₀), myosin phosphatase-targeting subunit 1 (MYPT1) and protein kinase C-potentiated inhibitory protein for heterotrimeric myosin light-chain phosphatase of 17 kDa (CPI17). Pretreatment with GA dose-dependently inhibited the concentration-response curves in response to sodium fluoride (NaF) or thromboxane A(2) agonist U46619, but not to phorbol 12, 13-dibutyrate (PDBu). GA decreased the activation of RhoA as well as the phosphorylation level of MLC₂₀, MYPT1(Thr₈₅₅), and CPI17 induced by 8.0 mM NaF or 30 nM U46619. However, K+ channel blockers such as glibenclamide, apamin, or charybdotoxin did not affect the vascular relaxation induced by GA. Furthermore, GA did not affect the level of phosphorylation of CPI17 induced by PDBu. GA reduces vascular contraction through inhibition of RhoA/Rho-kinase pathway in endothelium-denuded rat aorta.
Cardiovascular Research Institute, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
Young Mi
YM
Seok
Young Whan
YW
Choi
Gyung-Duck
GD
Kim
Hye Young
HY
Kim
Yoh
Y
Takuwa
In Kyeom
IK
Kim
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D034242:Cyclooctanes / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D054645:Protein Phosphatase 1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D012969:Sodium Fluoride / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D034242:Cyclooctanes; D004149:Dioxoles; D007211:Indoles; D017705:Lignans; D009124:Muscle Proteins; D018994:Myosin Light Chains; D010750:Phosphoproteins; D026902:Potassium Channel Blockers; C491519:Ppp1r14a protein, rat; D047428:Protein Kinase Inhibitors; D014665:Vasodilator Agents; D015240:Phorbol 12,13-Dibutyrate; C033585:schizandrol B; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D012969:Sodium Fluoride; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1; D020742:rhoA GTP-Binding Protein; C064758:Ro 31-8220