Effects of emodin on Ca2+ signal transduction of smooth muscle cells in multiple organ dysfunction syndrome.
We have made several reports on the signal transduction mechanism that emodin enhance the calcium concentrations of smooth muscle cells (SMCs) in the physiological condition by inositol [1, 4, 5]-friphosphate (IP3). The observation that IP3 concentrations in SMCs were decreased in multiple organ dysfunction syndrome (MODS) prompted us to ask whether emodin can activate SMCs to contract by way of elevating [Ca2+] and thus modulating the critical Ca2+ signal transduction pathways involved in the contraction of the SMCs in the pathological setting of MODS. To test this hypothesis, we used the rat model of MODS to explore the potential roles of emodin in Ca2+ signal transduction in the SMCs of colon in rats. ML-7 [an inhibitor of myosin light-chain kinase (MLCK)] and Calphostin C [an inhibitor of protein kinase C (PKC)] were used to observe the influence of emodin on the muscle strips and SMCs in rats after MODS. Nifedipine (an antagonist of voltage-gated Ca2+ channel), EGTA (removal of extracellular Ca2+), heparine (a specific IP3 receptor antagonist), and ryanodine were used to probe the potential mechanisms involved in emodin-mediated elevation of the global cytoplasmic Ca2+ in SMCs of colon in the rats after MODS. Our results show that emodin is capable of contract the smooth muscles of colon in rats after MODS by MLCK increasing [Ca2+] of SMCs, and by PKC enhancing the calcium sensitivity of SMCs. The mechanism by which emodin triggers elevated [Ca2+] of smooth muscles of colon in rats after MODS is likely to operate through IP3 and RyR receptors in the sarcoplasm. It is hoped that deeper insights into how emodin modulates the critical calcium signaling in SMCs might lead to the potential development of emodin in the treatment of MODS.
Zheyu
Chen
C
Department of General Surgery of West China Hospital, Sichuan University, Chengdu, China.
Qinghui
Q I
QI
Lixin
Liu
L
Tao
M A
MA
Xu
Jian
J
Zhang
Liang
L
Lunan
Yan
Y
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D003106:Colon / Q000502:physiology; D004642:Emodin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D009102:Multiple Organ Failure / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D011493:Protein Kinase C; D004642:Emodin