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1
Physiological antagonism between ventricular beta 1-adrenoceptors and alpha 1-adrenoceptors but no evidence for beta 2- and beta 3-adrenoceptor function in murine heart.小鼠心脏中室性β1-肾上腺素能受体与α1-肾上腺素能受体之间存在生理性拮抗作用，但未发现β2-和β3-肾上腺素能受体功能的证据。
Br J Pharmacol. 2002 May;136(2):217-29. doi: 10.1038/sj.bjp.0704700.
2
Cardiostimulant and cardiodepressant effects through overexpressed human beta2-adrenoceptors in murine heart: regional differences and functional role of beta1-adrenoceptors.通过在小鼠心脏中过表达人β2肾上腺素能受体产生的心脏刺激和心脏抑制作用：β1肾上腺素能受体的区域差异和功能作用
Naunyn Schmiedebergs Arch Pharmacol. 2003 Apr;367(4):380-90. doi: 10.1007/s00210-002-0681-4. Epub 2003 Mar 4.
3
Pertussis toxin suppresses carbachol-evoked cardiodepression but does not modify cardiostimulation mediated through beta1- and putative beta4-adrenoceptors in mouse left atria: no evidence for beta2- and beta3-adrenoreceptor function.百日咳毒素可抑制卡巴胆碱诱发的心脏抑制，但不改变通过小鼠左心房β1-和假定的β4-肾上腺素能受体介导的心脏刺激：无β2-和β3-肾上腺素能受体功能的证据。
Naunyn Schmiedebergs Arch Pharmacol. 2000 Feb;361(2):134-45. doi: 10.1007/s002109900156.
4
Phosphodiesterase-4 blunts inotropism and arrhythmias but not sinoatrial tachycardia of (-)-adrenaline mediated through mouse cardiac beta(1)-adrenoceptors.磷酸二酯酶-4可减弱由小鼠心脏β(1)-肾上腺素能受体介导的(-)-肾上腺素所引起的心肌收缩力和心律失常，但对窦房性心动过速无影响。
Br J Pharmacol. 2008 Feb;153(4):710-20. doi: 10.1038/sj.bjp.0707631. Epub 2007 Dec 17.
5
Function of cardiac beta1- and beta2-adrenoceptors of newborn piglets: role of phosphodiesterases PDE3 and PDE4.新生仔猪心脏β1-和β2-肾上腺素能受体的功能：磷酸二酯酶 PDE3 和 PDE4 的作用。
Eur J Pharmacol. 2010 Jul 25;638(1-3):99-107. doi: 10.1016/j.ejphar.2010.04.013. Epub 2010 Apr 18.
6
(-)-Adrenaline elicits positive inotropic, lusitropic, and biochemical effects through beta2 -adrenoceptors in human atrial myocardium from nonfailing and failing hearts, consistent with Gs coupling but not with Gi coupling.（-）-肾上腺素通过非衰竭和衰竭心脏的人心房心肌中的β2-肾上腺素能受体引发正性肌力、变时性和生化效应，这与Gs偶联一致，但与Gi偶联不一致。
Naunyn Schmiedebergs Arch Pharmacol. 2007 Mar;375(1):11-28. doi: 10.1007/s00210-007-0138-x. Epub 2007 Feb 13.
7
Differences between the third cardiac beta-adrenoceptor and the colonic beta 3-adrenoceptor in the rat.大鼠心脏第三种β-肾上腺素能受体与结肠β3-肾上腺素能受体之间的差异
Br J Pharmacol. 1996 Aug;118(8):2085-98. doi: 10.1111/j.1476-5381.1996.tb15648.x.
8
PDE3, but not PDE4, reduces β₁ - and β₂-adrenoceptor-mediated inotropic and lusitropic effects in failing ventricle from metoprolol-treated patients.PDE3，但不是 PDE4，可降低美托洛尔治疗患者衰竭心室中β₁-和β₂-肾上腺素能受体介导的变力和变时效应。
Br J Pharmacol. 2013 Jun;169(3):528-38. doi: 10.1111/bph.12167.
9
Do both adrenaline and noradrenaline stimulate cardiac alpha-adrenoceptors to induce positive inotropy of rat atria?肾上腺素和去甲肾上腺素都会刺激心脏α-肾上腺素能受体以诱导大鼠心房产生正性肌力作用吗？
Br J Pharmacol. 1989 Oct;98(2):597-611. doi: 10.1111/j.1476-5381.1989.tb12634.x.
10
Abolition of (-)-CGP 12177-evoked cardiostimulation in double beta1/beta2-adrenoceptor knockout mice. Obligatory role of beta1-adrenoceptors for putative beta4-adrenoceptor pharmacology.在双β1/β2肾上腺素能受体基因敲除小鼠中消除（-）-CGP 12177诱发的心脏刺激作用。β1肾上腺素能受体在假定的β4肾上腺素能受体药理学中的必要作用。
Naunyn Schmiedebergs Arch Pharmacol. 2001 Jan;363(1):87-93. doi: 10.1007/s002100000336.

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Microtubule-Mediated Regulation of βAR Translation and Function in Failing Hearts.微管介导线粒体 βAR 翻译和功能在衰竭心脏中的调节。
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Cardiac Cyclic Nucleotide Phosphodiesterases: Roles and Therapeutic Potential in Heart Failure.心脏环核苷酸磷酸二酯酶：心力衰竭中的作用和治疗潜力。
Cardiovasc Drugs Ther. 2020 Jun;34(3):401-417. doi: 10.1007/s10557-020-06959-1.
4
Cardiac β -adrenoceptors-A role in human pathophysiology?心脏β-肾上腺素能受体——在人类病理生理学中的作用？
Br J Pharmacol. 2019 Jul;176(14):2482-2495. doi: 10.1111/bph.14635. Epub 2019 Apr 22.
5
β 1 Adrenoceptor antagonistic effects of the supposedly selective β 2 adrenoceptor antagonist ICI 118,551 on the positive inotropic effect of adrenaline in murine hearts.β1 肾上腺素受体拮抗作用：所谓选择性β2 肾上腺素受体拮抗剂 ICI 118,551 对肾上腺素在鼠心正性肌力作用的影响。
Pharmacol Res Perspect. 2015 Oct;3(5):e00168. doi: 10.1002/prp2.168. Epub 2015 Jul 31.
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GPR55 deletion in mice leads to age-related ventricular dysfunction and impaired adrenoceptor-mediated inotropic responses.小鼠体内GPR55基因缺失会导致与年龄相关的心室功能障碍以及肾上腺素能受体介导的变力反应受损。
PLoS One. 2014 Oct 2;9(9):e108999. doi: 10.1371/journal.pone.0108999. eCollection 2014.
7
Non-classical regulation of β1- and β 2-adrenoceptor-mediated inotropic responses in rat heart ventricle by the G protein Gi.G蛋白Gi对大鼠心室β1和β2肾上腺素能受体介导的变力性反应的非经典调节
Naunyn Schmiedebergs Arch Pharmacol. 2014 Dec;387(12):1177-86. doi: 10.1007/s00210-014-1036-7. Epub 2014 Sep 13.
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Gi proteins regulate adenylyl cyclase activity independent of receptor activation.G蛋白独立于受体激活来调节腺苷酸环化酶的活性。
PLoS One. 2014 Sep 9;9(9):e106608. doi: 10.1371/journal.pone.0106608. eCollection 2014.
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Takotsubo cardiomyopathy.应激性心肌病
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10
Phosphodiesterases do not limit beta1-adrenoceptor-mediated sinoatrial tachycardia: evidence with PDE3 and PDE4 in rabbits and PDE1-5 in rats.磷酸二酯酶并不限制β1 - 肾上腺素能受体介导的窦性心动过速：兔中PDE3和PDE4以及大鼠中PDE1 - 5的证据。
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本文引用的文献

1
Comparison of the affinity of beta-blockers for two states of the beta 1-adrenoceptor in ferret ventricular myocardium.β受体阻滞剂对雪貂心室肌中β1肾上腺素能受体两种状态亲和力的比较。
Br J Pharmacol. 2002 Jan;135(2):451-61. doi: 10.1038/sj.bjp.0704450.
2
Beta-adrenergic receptor subtype-specific signaling in cardiac myocytes from beta(1) and beta(2) adrenoceptor knockout mice.来自β1和β2肾上腺素能受体基因敲除小鼠心肌细胞的β肾上腺素能受体亚型特异性信号传导
Mol Pharmacol. 2001 Sep;60(3):577-83.
3
Murine ventricular L-type Ca(2+) current is enhanced by zinterol via beta(1)-adrenoceptors, and is reduced in TG4 mice overexpressing the human beta(2)-adrenoceptor.小鼠心室L型钙电流通过齐帕特罗经β₁肾上腺素能受体增强，而在过表达人β₂肾上腺素能受体的TG4小鼠中则降低。
Br J Pharmacol. 2001 May;133(1):73-82. doi: 10.1038/sj.bjp.0704045.
4
Abolition of (-)-CGP 12177-evoked cardiostimulation in double beta1/beta2-adrenoceptor knockout mice. Obligatory role of beta1-adrenoceptors for putative beta4-adrenoceptor pharmacology.在双β1/β2肾上腺素能受体基因敲除小鼠中消除（-）-CGP 12177诱发的心脏刺激作用。β1肾上腺素能受体在假定的β4肾上腺素能受体药理学中的必要作用。
Naunyn Schmiedebergs Arch Pharmacol. 2001 Jan;363(1):87-93. doi: 10.1007/s002100000336.
5
alpha-Adrenoceptor stimulation-mediated negative inotropism and enhanced Na(+)/Ca(2+) exchange in mouse ventricle.α-肾上腺素能受体刺激介导的小鼠心室负性肌力作用及增强的Na⁺/Ca²⁺交换
Am J Physiol Heart Circ Physiol. 2001 Jan;280(1):H132-41. doi: 10.1152/ajpheart.2001.280.1.H132.
6
Beta(2)-adrenergic and several other G protein-coupled receptors in human atrial membranes activate both G(s) and G(i).人心房膜中的β(2)-肾上腺素能受体和其他几种G蛋白偶联受体可同时激活G(s)和G(i)。
Circ Res. 2000 Oct 13;87(8):705-9. doi: 10.1161/01.res.87.8.705.
7
Both beta(2)- and beta(1)-adrenergic receptors mediate hastened relaxation and phosphorylation of phospholamban and troponin I in ventricular myocardium of Fallot infants, consistent with selective coupling of beta(2)-adrenergic receptors to G(s)-protein.β₂-和β₁-肾上腺素能受体均介导法洛四联症患儿心室心肌中受磷蛋白和肌钙蛋白I的加速舒张和磷酸化，这与β₂-肾上腺素能受体与G(s)蛋白的选择性偶联一致。
Circulation. 2000 Oct 10;102(15):1814-21. doi: 10.1161/01.cir.102.15.1814.
8
Characterization of G-protein signaling in ventricular myocytes from the adult mouse heart: differences from the rat.成年小鼠心脏心室肌细胞中G蛋白信号转导的特征：与大鼠的差异。
J Mol Cell Cardiol. 2000 Jul;32(7):1211-21. doi: 10.1006/jmcc.2000.1156.
9
Coupling function of endogenous alpha(1)- and beta-adrenergic receptors in mouse cardiomyocytes.小鼠心肌细胞中内源性α(1) - 和β - 肾上腺素能受体的偶联功能。
Circ Res. 2000 May 26;86(10):1047-53. doi: 10.1161/01.res.86.10.1047.
10
Pertussis toxin suppresses carbachol-evoked cardiodepression but does not modify cardiostimulation mediated through beta1- and putative beta4-adrenoceptors in mouse left atria: no evidence for beta2- and beta3-adrenoreceptor function.百日咳毒素可抑制卡巴胆碱诱发的心脏抑制，但不改变通过小鼠左心房β1-和假定的β4-肾上腺素能受体介导的心脏刺激：无β2-和β3-肾上腺素能受体功能的证据。
Naunyn Schmiedebergs Arch Pharmacol. 2000 Feb;361(2):134-45. doi: 10.1007/s002109900156.

小鼠心脏中室性β1-肾上腺素能受体与α1-肾上腺素能受体之间存在生理性拮抗作用，但未发现β2-和β3-肾上腺素能受体功能的证据。

Physiological antagonism between ventricular beta 1-adrenoceptors and alpha 1-adrenoceptors but no evidence for beta 2- and beta 3-adrenoceptor function in murine heart.

作者信息

Heubach Jürgen F, Rau Thomas, Eschenhagen Thomas, Ravens Ursula, Kaumann Alberto J

机构信息

Institut für Pharmakologie und Toxikologie, Medizinische Fakultät Carl Gustav Carus der TU Dresden, D-01307 Dresden, Germany.

出版信息

Br J Pharmacol. 2002 May;136(2):217-29. doi: 10.1038/sj.bjp.0704700.

DOI:10.1038/sj.bjp.0704700
PMID:12010770
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1573340/
Abstract
  1. Murine left atrium lacks inotropic beta(2)-adrenoceptor function. We investigated whether beta(2)-adrenoceptors are involved in the cardiostimulant effects of (-)-adrenaline on spontaneously beating right atria and paced right ventricular myocardium of C57BL6 mice. We also studied a negative inotropic effect of (-)-adrenaline. 2. Sinoatrial tachycardia, evoked by (-)-adrenaline was resistant to blockade by beta(2)-selective ICI 118,551 (50 nM) but antagonized by beta(1)-selective CGP 20712A (300 nM). This pattern was unaffected by pretreatment with pertussis toxin (PTX, 600 microg kg(-1) i.p. 24 h) which reversed carbachol-evoked bradycardia to tachycardia. 3. Increases of ventricular force by (-)-adrenaline and (-)-noradrenaline were not blocked by ICI 118,551 but antagonized by CGP 20712A. 4. Under blockade of beta-adrenoceptors, (-)-adrenaline and (-)-noradrenaline depressed ventricular force (-logIC(50)M=7.7 and 6.9). The cardiodepressant effects of (-)-adrenaline were antagonized by phentolamine (1 microM) and prazosin (1 microM) but not by (-)-bupranolol (1 microM). Prazosin potentiated the positive inotropic effects of (-)-adrenaline (in the absence of beta-blockers) from -logEC(50)M=6.2 - 6.8. 5. PTX-treatment reduced carbachol-evoked depression of ventricular force in the presence of high catecholamine concentrations. Inhibition of ventricular function of G(i) protein was verified by 82% reduction of in vitro ADP-ribosylation. PTX-treatment tended to increase the positive inotropic potency of (-)-adrenaline under all conditions investigated, including the presence of ICI 118,551. 6. (-)-Adrenaline causes murine cardiostimulation through beta(1)-adrenoceptors but not through beta(2)-adrenoceptors. The negative inotropic effects of (-)-adrenaline are mediated through ventricular alpha(1)-adrenoceptors but not through beta(3)-adrenoceptors. Both G(i) protein and alpha(1)-adrenoceptors restrain (-)-adrenaline-evoked increases in right ventricular force mediated through beta(1)-adrenoceptors.
摘要
  1. 小鼠左心房缺乏变力性β(2)-肾上腺素能受体功能。我们研究了β(2)-肾上腺素能受体是否参与(-)-肾上腺素对C57BL6小鼠自发性搏动的右心房和起搏的右心室心肌的心脏刺激作用。我们还研究了(-)-肾上腺素的负性变力作用。2. (-)-肾上腺素诱发的窦性心动过速对β(2)-选择性ICI 118,551（50 nM）的阻断有抗性，但可被β(1)-选择性CGP 20712A（300 nM）拮抗。这种模式不受百日咳毒素（PTX，600 μg kg(-1)腹腔注射，24小时）预处理的影响，PTX可使卡巴胆碱诱发的心动过缓转变为心动过速。3. (-)-肾上腺素和(-)-去甲肾上腺素引起的心室力增加未被ICI 118,551阻断，但被CGP 20712A拮抗。4. 在β-肾上腺素能受体阻断下，(-)-肾上腺素和(-)-去甲肾上腺素降低心室力（-logIC(50)M = 7.7和6.9）。(-)-肾上腺素的心脏抑制作用被酚妥拉明（1 μM）和哌唑嗪（1 μM）拮抗，但不被(-)-布普洛尔（1 μM）拮抗。哌唑嗪增强了(-)-肾上腺素（在无β-阻滞剂时）的正性变力作用，从-logEC(50)M = 6.2提高到6.8。5. PTX处理在高儿茶酚胺浓度存在时减少了卡巴胆碱诱发的心室力抑制。通过体外ADP-核糖基化减少82%证实了G(i)蛋白对心室功能的抑制。在所有研究条件下，包括存在ICI 118,551时，PTX处理倾向于增加(-)-肾上腺素的正性变力效力。6. (-)-肾上腺素通过β(1)-肾上腺素能受体而非β(2)-肾上腺素能受体引起小鼠心脏刺激。(-)-肾上腺素的负性变力作用通过心室α(1)-肾上腺素能受体而非β(3)-肾上腺素能受体介导。G(i)蛋白和α(1)-肾上腺素能受体均抑制通过β(1)-肾上腺素能受体介导的(-)-肾上腺素诱发的右心室力增加。