Study on mechanisms of κ-opioid receptor agonist affects neonatal rat myocardial hypertrophy induced by isoproterenol

Abstract

Abstract: AIM: To study the mechanisms of effects of the κ-opioid receptor (κ-OR) on neonatal rat hypertrophic myocardial cells induced by isoproterenol (ISO). METHODS: Myocardial cells of neonatal rats were cultured in vitro.The total protein content was detected by the Lowry's assay.The volume of myocardial cell was measured by computer photogragh analysis system and the protein synthesis was assayed with [³H] leucine intake method.The degree of extracellular signal-regulated kinase (ERK) phosphorylation was determined by western- blotting.RESULTS: U0126(an inhibitor of ERK) decreased the total protein content, the cell size, the[³H] leucine incorporation and the ERK phosphorylation degree in hypertrophic myocardial cells induced by ISO.1 μmol/L U50, 488H(a κ-opioid receptor antagonist) could decrease the total protein content, the cell size, the[³H] leucine incorporation and the degree of ERK phosphorylation.But these effects could be diminished when incubated with U0126. CONCLUSION: κ-opioid can abolish the hypertrophic response induced by ISO of cardiac myocytes, which was associate with ERK pathway.The inhibitor of ERK significantly inhibits the ISO-induced hypertrophied effect.

Key words: κ-opioid, β-receptor, myocardial hypertrophy, extracellular signal-regulated kinase

CLC Number:

R965.2

CUI Lei, WANG Hong-xin, ZHAO Min. Study on mechanisms of κ-opioid receptor agonist affects neonatal rat myocardial hypertrophy induced by isoproterenol[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(9): 1042-1046.

References

1 Caffrey JL, Boluyt MO, Younes A, et al.Aging, cardiac proenkephalin mRNA and enkephalin peptides in the F344 rat [J]. J Mol Cell Cardiol, 1994;26 :701-711.
2 Springhorn JP, C1aycomb WC.Translation of heart preproenkephalin mRNA and secretion of enkephalin peptides from cultured cardiac myocytes [J].Am J Physiol, 1992;263 (5Pt2) : H1560-H1566.
3 Wong TM, Wu S.Roles of kappa opioid receptors in cardioprotection against ischemia-the signaling mechanisms [J].Acta Physiol Sin, 2003;55 :115-120.
4 Utz J, Eckert R, Trautwein W, et al.Inhibition of L-type calcium current in guinea pig ventricular myocytes by kappa-opioid agonist U50, 488H does not involve binding to opiate receptors [J].J Pharmacol Exp Ther, 1995;274 :627-633.
5 Yu XC, Li HY, Wang HX, et al.U50, 488H inhibits effect of Norepinephrine in rat cardiomyocytes-Cross talk between κ-OR and β-adrenergic receptors [J].JMol Cell Cardiol, 1998;30:405-413.
6 Burt AR, Carr IC, Mullaney I, et al.Agonist activation of p42 and p44 mitogen-activated protein kinase following expression of the mouse d opioid receptor in Rat-1 fibroblasts:effects of receptor expression levels and comparisons with G-protein activation [J].Biochem J, 1996;320:227-235.
7 王洪新, 陶亮, 饶曼人.血管紧张素Ⅱ 对培养乳鼠心脏的非心肌细胞DNA 及蛋白合成的影响 [J].中国药理学通报, 1996;12 :417-420.
8 Messerli FH, Aristizabal D, Soria F, et al.Reduction of left ventricular hypertrophy :How beneficial [J] Am Heart J, 1993;125(5 Pt 2) :1520-1524.
9 levy D, Garrison RJ, Savage DD, et al.Prognostic implications of echocardiographically determined left ventricular mass in the Framingham heart study [J].N Engl JMed, 1990;323:1706-1707.
10 单丹, 王洪新, 苏玉虹, 等.κ-受体与肾上腺素受体交互作用抑制心肌细胞肥大 [J].中国临床药理学与治疗学, 2005;10 :537-541.
11 Yu XC, Wang HX, Pei JM, et al.Anti-arrhythmic effect of Kappa-opioid receptor stimulation in the perfused rat heart :involvement of a cAMP-dependent pathway [J].J Mol Cell Cardiol, 1999;31:1809-1819.
12 Smith RJ, Sam LM, Justen JM, et al.Receptor-coupled signal transduction in human polymorphonuclear neutrophils:effects of a novel inhibitor phospholipase C-dependent processes on cell responsiveness [J].J Pharmcol Exp Ther, 1990;253:688.
13 Lei I, Kishore BS, Paclua R, et al.Adult cardiomyocytes repriss function high-affility receptors for basic fibroblast growth factor [J].Am J Physiol, 1995;268:H1927-H1938.

[1]	PENG Juan, LI Ranyi, FAN Linlin, LI Xiaoyu, LV Qianzhou, ZOU Yunzeng. Progress of pharmacotherapy for myocardial hypertrophy and cardiac remodeling [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(4): 382-389.
[2]	HUANG Jin-xian, ZHOU Si-gui. Research progress of fenofibrate in the mechanism of myocardial hypertrophy [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(3): 356-360.
[3]	DAI Heng, ZUO Zhong, CHEN Ping, GAO Jin, XIONG Qiu-ju. Influence of prostaglandin E2 on hypertrophy in H9c2 cardiac cells [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(7): 721-724.
[4]	ZHU Hai-long, ZHANG Gen-bao, LI Wei, ZHANG Cui. Protective effects of ERK1/2 inhibitor PD98059 on multiple organ dysfunction in disseminated- intravascular-coagulation rat [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(2): 159-163.
[5]	XIONG Qi-ru, XIA Jun, LI Li-xiang, QIAN Ye-ben, YU Hong-zhu, XU Ye-chuan. Effects of lipoxygenase inhibitor on proliferation of HepG2 cell line and MEK/ERK signaling pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(1): 1-5.
[6]	TIAN He-ping, GU Bin, CHENG Feng, HAO Huai-yong, HU Wei-xin, LI Li-xin. Nimodipine inhibits ischemia-reperfusion triggered neurogenesis in adult rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(1): 32-36.
[7]	. Effects of breviscapin on isoproterenol-induced myocardial hypertrophy in mice [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(3): 273-276.
[8]	LIANG Xu-guo, ZHANG Xiu-mei. Effect of combination of ACEI and ARB on left ventricle in pressure-overloaded hypertrophy rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(10): 1133-1136.
[9]	CHEN Chun-Fu, CAO Bing-Zhen, SHEN Jun, CHANG Gao-Feng, SHANG Ming-Qian, CAO xia, JIN Shan, LU Wei. Randomized and contrast study on the combined effects of three antihypertensive drugs in the patients with subcortical arteriosclerotic encephalopaphy [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2002, 7(6): 504-507.