Genetic disruption of G proteins, Gi2α or Goα, does not abolish inotropic and chronotropic effects of stimulating muscarinic cholinoceptors in atrium
作者： P Boknik , S Grote-Wessels , G Barteska , M Jiang , FU Müller
DOI: 10.1111/J.1476-5381.2009.00441.X
关键词: Muscarinic acetylcholine receptor 、 Internal medicine 、 Stimulation 、 Atrium (architecture) 、 G protein 、 Endocrinology 、 Chronotropic 、 Carbachol 、 Pertussis toxin 、 Isoprenaline 、 Chemistry
摘要: Background and purpose: Classically, stimulation of muscarinic cholinoceptors exerts negative inotropic chronotropic effects in the atrium mammalian hearts. These are crucial to vagal regulation heart beat. This effect is assumed be mediated via GTP binding (G) proteins, because they can abolished by Pertussis toxin. However, it unknown which G proteins involved. Experimental approach: We studied contractility isolated left or right from genetically manipulated mice with deletion one two either α subunit Gi2 protein (Gi2α) Go (Goα). Preparations were stimulated carbachol alone after pretreatment β-adrenoceptor agonist isoprenaline. For comparison, on L-type Ca2+-channels ventricular cardiomyocytes studied. Key results: The presence isoprenaline identical atria knockout wild-type mice. isoprenaline-activated Ca2+-channel was greatly attenuated both types studied. Conclusions implications: data imply that there redundancy for signal transduction toxin-sensitive other than Gi2α Goα mediate atrium. Moreover, different ventricle compared
sci-hub.se 参考文章(54)
Ramesh C. Gupta, Joachim Neumann, August M. Watanabe, Hani N. Sabbah1, Muscarinic-cholinoceptor mediated attenuation of phospholamban phosphorylation induced by inhibition of phosphodiesterase in ventricular cardiomyocytes: Evidence against a cAMP- dependent effect Molecular and Cellular Biochemistry. ,vol. 187, pp. 155- 161 ,(1998) , 10.1023/A:1006899931151
A J Pappano, K Löffelholz, The parasympathetic neuroeffector junction of the heart. Pharmacological Reviews. ,vol. 37, pp. 1- 24 ,(1985)
Z Ahmad, F J Green, H S Subuhi, A M Watanabe, Autonomic regulation of type 1 protein phosphatase in cardiac muscle. Journal of Biological Chemistry. ,vol. 264, pp. 3859- 3863 ,(1989) , 10.1016/S0021-9258(19)84930-X
J P Lindemann, A M Watanabe, Muscarinic cholinergic inhibition of beta-adrenergic stimulation of phospholamban phosphorylation and Ca2+ transport in guinea pig ventricles. Journal of Biological Chemistry. ,vol. 260, pp. 13122- 13129 ,(1985) , 10.1016/S0021-9258(17)38847-6
Huizhen Wang, Hong Han, Liming Zhang, Hong Shi, Gernot Schram, Stanley Nattel, Zhiguo Wang, Expression of multiple subtypes of muscarinic receptors and cellular distribution in the human heart. Molecular Pharmacology. ,vol. 59, pp. 1029- 1036 ,(2001) , 10.1124/MOL.59.5.1029
Jesus Gomeza, Peter W. Stengel, Jurgen Wess, Marlene L. Cohen, M2 and M4 Receptor Knockout Mice: Muscarinic Receptor Function in Cardiac and Smooth Muscle In Vitro Journal of Pharmacology and Experimental Therapeutics. ,vol. 292, pp. 877- 885 ,(2000)
Otto-Erich Brodde, Martin C. Michel, Adrenergic and Muscarinic Receptors in the Human Heart Pharmacological Reviews. ,vol. 51, pp. 651- 690 ,(1999)
Fuhua Chen, Karsten Spicher, Meisheng Jiang, Lutz Birnbaumer, Glenn T. Wetzel, Lack of muscarinic regulation of Ca2+ channels in Gi2α gene knockout mouse hearts American Journal of Physiology-heart and Circulatory Physiology. ,vol. 280, ,(2001) , 10.1152/AJPHEART.2001.280.5.H1989
Masao Endoh, Muscarinic regulation of Ca2+ signaling in mammalian atrial and ventricular myocardium. European Journal of Pharmacology. ,vol. 375, pp. 177- 196 ,(1999) , 10.1016/S0014-2999(99)00231-9
R C Gupta, J Neumann, P Durant, A M Watanabe, A1-adenosine receptor-mediated inhibition of isoproterenol-stimulated protein phosphorylation in ventricular myocytes. Evidence against a cAMP-dependent effect. Circulation Research. ,vol. 72, pp. 65- 74 ,(1993) , 10.1161/01.RES.72.1.65