title: Propofol reduced myocardial contraction of vertebrates partly by mediating the cyclic AMP-dependent protein kinase phosphorylation pathway.
abstract: Propofol inhibits myocardial contraction in a dose dependent manner. The present study is designed to examine the effect of propofol on PKA mediated myocardial contraction in the absence of adrenoreceptor agonist. The contraction of isolated rat heart was measured in the presence or absence of PKA inhibitor H89 or propofol, using a pressure transducer. The levels of cAMP and PKA kinase activity were detected by ELISA. The mRNA and total protein or phosphorylation level of PKA and downstream proteins were tested in the presence or absence of PKA inhibitor H89 or propofol, using RT-PCR, QPCR and western blotting. The phosphorylation level of PKA was examined thoroughly using immunofluorescence and PKA activity non-radioactive detection kit. Propofol induced a dose-dependent negative contractile response on the rat heart. The inhibitory effect of high concentration propofol (50μM) with 45% decease of control could be partly reversed by the PKA inhibitor H89 (10μM) and the depressant effect of propofol decreased from 45% to 10%. PKA kinase activity was inhibited by propofol in a dose-dependent manner. Propofol also induced a decrease in phosphorylation of PKA, which was also inhibited by H89, but did not alter the production of cAMP and the mRNA levels of PKA. The downstream proteins of PKA, PLN and RyR2 were phosphorylated to a lesser extent with propofol or H89 than control. These results demonstrated that propofol induced a negative myocardial contractile response partly by mediating the PKA phosphorylation pathway.
authors: Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China.
authors: Xiaotong
authors: X
authors: Sun
authors: Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China.
authors: Xinyu
authors: X
authors: Zhang
authors: Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China.
authors: Qiyu
authors: Q
authors: Bo
authors: Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China.
authors: Tao
authors: T
authors: Meng
authors: Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China.
authors: Zhen
authors: Z
authors: Lei
authors: Department of Physiology, Shandong University School of Medicine, Jinan, China.
authors: Jingxin
authors: J
authors: Li
authors: Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China.
authors: Yonghao
authors: Y
authors: Hou
authors: Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China.
authors: Xiaoqian
authors: X
authors: Yu
authors: Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China. Electronic address: yujingui1109@126.com.
authors: Jingui
authors: J
authors: Yu
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010766:Phosphorylation; D015742:Propofol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D011941:Receptors, Adrenergic; D017868:Cyclic AMP-Dependent Protein Kinases; D015742:Propofol
keywords: Myocardial contraction; PKA; Phosphorylation; Propofol