钙敏感受体在心血管生理和疾病中的作用
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摘要
钙敏感受体(calcium sensing receptor,CaSR)是G蛋白偶联受体(GPCRs)C家族成员之一,能被Ca~(2+)、Mg~(2+)、氨基酸、多胺等激活,它是公认的具有广泛表达功能的受体,在甲状旁腺、肾脏、肠道、骨骼系统高度表达,也在心血管系统的不同组织中表达,发挥不同作用,从而参与心血管系统的生理病理过程。本综述是概述CaSR对心血管系统的重要性。
Calcium sensing receptor(CaSR), a member of the G protein coupled receptor(GPCRs) C family, can be activated by Ca~(2+) Mg~(2+), amino acids, and polyamines. It is now recognized as an ubiquitously expressed receptor and is highly expressed in the parathyroid gland, kidneys, intestinal system, and skeletal system. It also plays different roles in different tissues of the cardiovascular system and participates in physiological and pathological processes of the cardiovascular system. The focus of this review is to summarize the importance of CaSR in the cardiovascular system.
Calcium sensing receptor(CaSR), a member of the G protein coupled receptor(GPCRs) C family, can be activated by Ca~(2+) Mg~(2+), amino acids, and polyamines. It is now recognized as an ubiquitously expressed receptor and is highly expressed in the parathyroid gland, kidneys, intestinal system, and skeletal system. It also plays different roles in different tissues of the cardiovascular system and participates in physiological and pathological processes of the cardiovascular system. The focus of this review is to summarize the importance of CaSR in the cardiovascular system.
引文
[1] Tfelt-Hansen J,Brown EM.The calcium-sensing receptor in normal physiology and pathophysiology:a review[J].Crit Rev Clin Lab Sci,2017,17(1):35-70.
[2] Hendy GN,Guarnieri V,Canaff L.Calcium-sensing receptor and associated diseases[J].Prog Mol Biol Transl Sci,2009,89(89):31-95.
[3] Hu J,Spiegel AM.Naturally occurring mutations of the extracellular Ca2+-sensing receptor:implications for its structure and function[J].Trends Endocrinol Metab,2003,14(6):282-288.
[4] Filopanti M,Corbetta S,Barbieri A,et al.Pharmacology of the calcium sensing receptor[J].Clin Cases Miner Bone Metab,2013,10(3):162-165.
[5] Brown EM.Extracellular Ca2+ sensing,regulation of parathyroid cell function,androle of Ca2+ and other ions as extracellular (first) messengers[J].Physiol Rev,1991,71(71):371-411.
[6] Houillier P.Calcium-sensing in the kidney[J].Curr Opin Nephrol Hypertens,2013,22(5):566-571.
[7] Tang L,Cheng CY,Sun X,et al.The Extracellular Calcium-Sensing Receptor in the Intestine:Evidence for Regulation of Colonic Absorption,Secretion,Motility,and Immunity[J].Front Physiol,2016,7:245.
[8] Lu B,Zhang Q,Wang H,et al.Extracellular calcium controls background current and neuronal excitability via an UNC79-UNC80-NALCN cation channel complex[J].Neuron,2010,68(3):488-499.
[9] Alfadda TI,Saleh AM,Houillier P,et al.Calcium-sensing receptor 20 years later[J].Am J Physiol Cell Physiol,2014,307(3):221-231.
[10]Bukoski RD,Bian K,Wang Y,et al.Perivascular sensory nerve Ca2+ receptor and Ca2+-induced relaxation of isolated arteries[J].Hypertension,1997,30(6):1431-1439.
[11]Ishioka N,Bukoski RD.A Role for N-Arachidonylethanolamine (Anandamide) as the Mediator of Sensory Nerve-Dependent Ca2+-Induced Relaxation[J].J Pharmacol Exp Ther,1999,289(1):245-250.
[12]Weston AH,Absi M,Ward DT,et al.Evidence in favor of a calcium-sensing receptor in arterial endothelial cells:studies with calindol and Calhex 231[J].Circ Res,2005,97(4):391-398.
[13]Ziegelstein RC,Xiong Y,He C,et al.Expression of a functional extracellular calcium-sensing receptor in human aortic endothelial cells[J].Biochem Biophys Res Commun,2006,342(1):153-163.
[14]Wonneberger K,Scofield MA,Wangemann P.Evidence for a calcium-sensing receptor in the vascular smooth muscle cells of the spiral modiolar artery[J].J Membr Biol,2000,175(3):203-212.
[15]Schepelmann M,Yarova PL,Lopez-Fernandez I,et al.The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure[J].Am J Physiol Cell Physiol,2016,310(3):193-204.
[16]Farzaneh-Far A,Proudfoot D,Weissberg PL,et al.Matrix gla protein is regulated by a mechanism functionally related to the calcium-sensing receptor[J].Biochem Biophys Res Commun,2000,277(3):736-740.
[17]Alam MU,Kirton JP,Wilkinson FL,et al.Calcification is associated with loss of functional calcium-sensing receptor in vascular smooth muscle cells[J].Cardiovasc Res,2009,81(2):260-268.
[18]Mary A,Hénaut L,Boudot C,et al.Calcitriol prevents in vitro vascular smooth muscle cell mineralization by regulating calcium-sensing receptor expression[J].Endocrinology,2015,156(6):1965-1974.
[19]Wang R,Xu C,Zhao W,et al.Calcium and polyamine regulated calcium-sensing receptors in cardiac tissues[J].Eur J Biochem,2010,270(12):2680-2688.
[20]Schreckenberg R,Dyukova E,Sitdikova G,et al.Mechanisms by which calcium receptor stimulation modifies electro-mechanical coupling in isolated ventricular cardiomyocytes[J].Pflugers Arch,2015,467(2):379-388.
[21]Bai SZ,Sun J,Wu H,et al.Decrease in calcium-sensing receptor in the progress of diabetic cardiomyopathy[J].Diabetes Res Clin Pract,2012,95(3):378-385.
[22]Sun J,Murphy E.Calcium-sensing receptor:a sensor and mediator of ischemic preconditioning in the heart[J].Am J Physiol Heart Circ Physiol,2010,299(5):1309-1317.
[23]Dyukova E,Schreckenberg R,Arens C,et al.The Role of Calcium-Sensing Receptors in Endothelin-1-Dependent Effects on Adult Rat Ventricular Cardiomyocytes:Possible Contribution to Adaptive Myocardial Hypertrophy[J].J Cell Physiol,2017,232(9):2508-2518.
[24]Liu CH,Chang HK,Lee SP,et al.Activation of the Ca2+-sensing receptors increases currents through inward rectifier K+ channels via activation of phosphatidylinositol 4-kinase[J].Pflugers Arch,2016,468(11):1931-1943.
[25]Zhao YJ,Xu CQ,Zhang WH,et al.Role of polyamines in myocardial ischemia/reperfusion injury and their interactions with nitric oxide[J].Eur J Pharmacol,2007,562 (3):236-246.
[26]Dyukova E,Schreckenberg R,Sitdikova G,et al.Influence of Ischemic Pre-and Post-Conditioning on Cardiac Expression of Calcium-Sensing Receptor[J].BioNanoSci,2017,7(1):1-3.
[27]Zhang J,Zhou J,Cai L,et al.Extracellular calcium-sensing receptor is critical in hypoxic pulmonary vasoconstriction[J].Antioxid Redox Signal,2012,17(3):471-484.
[28]Yamamura A,Yagi S,Ohara N,et al.Calcilytics enhance sildenafil-induced antiproliferation in idiopathic pulmonary arterial hypertension[J].Eur J Pharmacol,2016,784:15-21.
[29]Wang LN,Wang C,Lin Y,et al.Involvement of calcium-sensing receptor in cardiac hypertrophy-induced by angiotensinII through calcineurin pathway in cultured neonatal rat cardiomyocytes[J].Biochem Biophys Res Commun,2008,369(2):584-589.
[30]Liu L,Wang C,Lin Y,et al.Suppression of calcium-sensing receptor ameliorates cardiac hypertrophy through inhibition of autophagy[J].Mol Med Rep,2016,14 (1):111-120.
[31]M?rlein C,Schreckenberg R,Schlüter KD.Basal ornithine decarboxylase activity modifies apoptotic and hypertrophic marker expression in post-ischemic hearts[J].Open Heart Failure Journal,2010,3(2):31-36.
[32]Jiang CM,Xu CQ,Mi Y,et al.Calcium-Sensing Receptor Induced Myocardial Ischemia/Reperfusion Injury via the C-Jun NH2-Terminal Protein Kinase Pathway[J].Molecular Cardiology Acta Cardiol Sin,2010,26(2):102-110.
[33]Chen W,Wang R,Chen B,et al.The ryanodine receptor store-sensing gate controls Ca2+ waves and Ca2+-triggered arrhythmias[J].Nat Med,2014,20(2):184-192.
[34]Zhang C,Miller CL,Brown EM,et al.The calcium sensing receptor:from calcium sensing to signaling [J].Sci China Life Sci,58(2015):14-27.
[35]黄侠,赵明.缝隙连接蛋白和心房颤动的研究进展[J].心肺血管病杂志,2015,34(5):419-421.
[36]李海涛.钙敏感受体激活对缺血再灌注兔心脏电生理特性的影响[J].郑州大学学报(医学版),2013,48(6):740-743.
[37]Klein GL,Enkhbaatar P,Traber DL,et al.Cardiovascular distribution of the calcium sensing receptor before and after burns[J].Burns,2008,34(3):370-375.
[38]Zhang X,Zhang T,Wu J,et al.Calcium sensing receptor promotes cardiac fibroblast proliferation and extracellular matrix secretion[J].Cell Physiol Biochem,2014,33(3):557-568.
[39]Tfelt-Hansen J,Hansen JL,Smajilovic S,et al.Calcium receptor is functionally expressed in rat neonatal ventricular cardiomyocytes[J].Am J Physiol Heart Circ Physiol,2006,290(3):1165-1171.
[2] Hendy GN,Guarnieri V,Canaff L.Calcium-sensing receptor and associated diseases[J].Prog Mol Biol Transl Sci,2009,89(89):31-95.
[3] Hu J,Spiegel AM.Naturally occurring mutations of the extracellular Ca2+-sensing receptor:implications for its structure and function[J].Trends Endocrinol Metab,2003,14(6):282-288.
[4] Filopanti M,Corbetta S,Barbieri A,et al.Pharmacology of the calcium sensing receptor[J].Clin Cases Miner Bone Metab,2013,10(3):162-165.
[5] Brown EM.Extracellular Ca2+ sensing,regulation of parathyroid cell function,androle of Ca2+ and other ions as extracellular (first) messengers[J].Physiol Rev,1991,71(71):371-411.
[6] Houillier P.Calcium-sensing in the kidney[J].Curr Opin Nephrol Hypertens,2013,22(5):566-571.
[7] Tang L,Cheng CY,Sun X,et al.The Extracellular Calcium-Sensing Receptor in the Intestine:Evidence for Regulation of Colonic Absorption,Secretion,Motility,and Immunity[J].Front Physiol,2016,7:245.
[8] Lu B,Zhang Q,Wang H,et al.Extracellular calcium controls background current and neuronal excitability via an UNC79-UNC80-NALCN cation channel complex[J].Neuron,2010,68(3):488-499.
[9] Alfadda TI,Saleh AM,Houillier P,et al.Calcium-sensing receptor 20 years later[J].Am J Physiol Cell Physiol,2014,307(3):221-231.
[10]Bukoski RD,Bian K,Wang Y,et al.Perivascular sensory nerve Ca2+ receptor and Ca2+-induced relaxation of isolated arteries[J].Hypertension,1997,30(6):1431-1439.
[11]Ishioka N,Bukoski RD.A Role for N-Arachidonylethanolamine (Anandamide) as the Mediator of Sensory Nerve-Dependent Ca2+-Induced Relaxation[J].J Pharmacol Exp Ther,1999,289(1):245-250.
[12]Weston AH,Absi M,Ward DT,et al.Evidence in favor of a calcium-sensing receptor in arterial endothelial cells:studies with calindol and Calhex 231[J].Circ Res,2005,97(4):391-398.
[13]Ziegelstein RC,Xiong Y,He C,et al.Expression of a functional extracellular calcium-sensing receptor in human aortic endothelial cells[J].Biochem Biophys Res Commun,2006,342(1):153-163.
[14]Wonneberger K,Scofield MA,Wangemann P.Evidence for a calcium-sensing receptor in the vascular smooth muscle cells of the spiral modiolar artery[J].J Membr Biol,2000,175(3):203-212.
[15]Schepelmann M,Yarova PL,Lopez-Fernandez I,et al.The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure[J].Am J Physiol Cell Physiol,2016,310(3):193-204.
[16]Farzaneh-Far A,Proudfoot D,Weissberg PL,et al.Matrix gla protein is regulated by a mechanism functionally related to the calcium-sensing receptor[J].Biochem Biophys Res Commun,2000,277(3):736-740.
[17]Alam MU,Kirton JP,Wilkinson FL,et al.Calcification is associated with loss of functional calcium-sensing receptor in vascular smooth muscle cells[J].Cardiovasc Res,2009,81(2):260-268.
[18]Mary A,Hénaut L,Boudot C,et al.Calcitriol prevents in vitro vascular smooth muscle cell mineralization by regulating calcium-sensing receptor expression[J].Endocrinology,2015,156(6):1965-1974.
[19]Wang R,Xu C,Zhao W,et al.Calcium and polyamine regulated calcium-sensing receptors in cardiac tissues[J].Eur J Biochem,2010,270(12):2680-2688.
[20]Schreckenberg R,Dyukova E,Sitdikova G,et al.Mechanisms by which calcium receptor stimulation modifies electro-mechanical coupling in isolated ventricular cardiomyocytes[J].Pflugers Arch,2015,467(2):379-388.
[21]Bai SZ,Sun J,Wu H,et al.Decrease in calcium-sensing receptor in the progress of diabetic cardiomyopathy[J].Diabetes Res Clin Pract,2012,95(3):378-385.
[22]Sun J,Murphy E.Calcium-sensing receptor:a sensor and mediator of ischemic preconditioning in the heart[J].Am J Physiol Heart Circ Physiol,2010,299(5):1309-1317.
[23]Dyukova E,Schreckenberg R,Arens C,et al.The Role of Calcium-Sensing Receptors in Endothelin-1-Dependent Effects on Adult Rat Ventricular Cardiomyocytes:Possible Contribution to Adaptive Myocardial Hypertrophy[J].J Cell Physiol,2017,232(9):2508-2518.
[24]Liu CH,Chang HK,Lee SP,et al.Activation of the Ca2+-sensing receptors increases currents through inward rectifier K+ channels via activation of phosphatidylinositol 4-kinase[J].Pflugers Arch,2016,468(11):1931-1943.
[25]Zhao YJ,Xu CQ,Zhang WH,et al.Role of polyamines in myocardial ischemia/reperfusion injury and their interactions with nitric oxide[J].Eur J Pharmacol,2007,562 (3):236-246.
[26]Dyukova E,Schreckenberg R,Sitdikova G,et al.Influence of Ischemic Pre-and Post-Conditioning on Cardiac Expression of Calcium-Sensing Receptor[J].BioNanoSci,2017,7(1):1-3.
[27]Zhang J,Zhou J,Cai L,et al.Extracellular calcium-sensing receptor is critical in hypoxic pulmonary vasoconstriction[J].Antioxid Redox Signal,2012,17(3):471-484.
[28]Yamamura A,Yagi S,Ohara N,et al.Calcilytics enhance sildenafil-induced antiproliferation in idiopathic pulmonary arterial hypertension[J].Eur J Pharmacol,2016,784:15-21.
[29]Wang LN,Wang C,Lin Y,et al.Involvement of calcium-sensing receptor in cardiac hypertrophy-induced by angiotensinII through calcineurin pathway in cultured neonatal rat cardiomyocytes[J].Biochem Biophys Res Commun,2008,369(2):584-589.
[30]Liu L,Wang C,Lin Y,et al.Suppression of calcium-sensing receptor ameliorates cardiac hypertrophy through inhibition of autophagy[J].Mol Med Rep,2016,14 (1):111-120.
[31]M?rlein C,Schreckenberg R,Schlüter KD.Basal ornithine decarboxylase activity modifies apoptotic and hypertrophic marker expression in post-ischemic hearts[J].Open Heart Failure Journal,2010,3(2):31-36.
[32]Jiang CM,Xu CQ,Mi Y,et al.Calcium-Sensing Receptor Induced Myocardial Ischemia/Reperfusion Injury via the C-Jun NH2-Terminal Protein Kinase Pathway[J].Molecular Cardiology Acta Cardiol Sin,2010,26(2):102-110.
[33]Chen W,Wang R,Chen B,et al.The ryanodine receptor store-sensing gate controls Ca2+ waves and Ca2+-triggered arrhythmias[J].Nat Med,2014,20(2):184-192.
[34]Zhang C,Miller CL,Brown EM,et al.The calcium sensing receptor:from calcium sensing to signaling [J].Sci China Life Sci,58(2015):14-27.
[35]黄侠,赵明.缝隙连接蛋白和心房颤动的研究进展[J].心肺血管病杂志,2015,34(5):419-421.
[36]李海涛.钙敏感受体激活对缺血再灌注兔心脏电生理特性的影响[J].郑州大学学报(医学版),2013,48(6):740-743.
[37]Klein GL,Enkhbaatar P,Traber DL,et al.Cardiovascular distribution of the calcium sensing receptor before and after burns[J].Burns,2008,34(3):370-375.
[38]Zhang X,Zhang T,Wu J,et al.Calcium sensing receptor promotes cardiac fibroblast proliferation and extracellular matrix secretion[J].Cell Physiol Biochem,2014,33(3):557-568.
[39]Tfelt-Hansen J,Hansen JL,Smajilovic S,et al.Calcium receptor is functionally expressed in rat neonatal ventricular cardiomyocytes[J].Am J Physiol Heart Circ Physiol,2006,290(3):1165-1171.