Decrease in heart adrenoceptor gene expression and receptor number as compensatory tool for preserved heart function and biological rhythm in M(2) KO animals
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Atropine pharmacology MeSH
- Receptors, Adrenergic, beta-1 metabolism MeSH
- Receptors, Adrenergic, beta-2 metabolism MeSH
- Bradycardia physiopathology MeSH
- Ventricular Function, Left physiology MeSH
- Isoproterenol pharmacology MeSH
- Carbachol pharmacology MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Propranolol pharmacology MeSH
- Receptor, Muscarinic M2 genetics MeSH
- Gene Expression Regulation * MeSH
- Heart Rate physiology MeSH
- Heart Ventricles metabolism MeSH
- Protein Binding MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Atropine MeSH
- Receptors, Adrenergic, beta-1 MeSH
- Receptors, Adrenergic, beta-2 MeSH
- Isoproterenol MeSH
- Carbachol MeSH
- Propranolol MeSH
- Receptor, Muscarinic M2 MeSH
Muscarinic receptors (MR) are main cardioinhibitory receptors. We investigated the changes in gene expression, receptor number, echocardiography, muscarinic/adrenergic agonist/antagonist changes in heart rate (HR) and HR biorhythm in M(2) KO mice (mice lacking the main cardioinhibitory receptors) in the left ventricle (LV) and right ventricle (RV). We hypothesize that the disruption of M(2) MR, key players in parasympathetic bradycardia, would change the number of receptors with antagonistic effects on the heart (β(1)- and β(2)-adrenoceptors, BAR), while the function of the heart would be changed only marginally. We have found changes in LV, but not in RV: decrease in M(3) MR, β(1)- and β(2)-adrenoceptor gene expressions that were accompanied by a decrease in MR and BAR receptor binding. No changes were found both in LV systolic and diastolic function as assessed by echocardiography (e.g., similar LV end-systolic and end-diastolic diameter, fractional shortening, mitral flow characteristics, and maximal velocity in LV outflow tract). We have found only marginal changes in specific HR biorhythm parameters. The effects of isoprenaline and propranolol on HR were similar in WT and KO (but with lesser extent). Atropine was not able to increase HR in KO animals. Carbachol decreased the HR in WT but increased HR in KO, suggesting the presence of cardiostimulatory MR. Therefore, we can conclude that although the main cardioinhibitory receptors are not present in the heart, the function is not much affected. As possible mechanisms of almost normal cardiac function, the decreases of both β(1)- and β(2)-adrenoceptor gene expression and receptor binding should be considered.
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Naunyn Schmiedebergs Arch Pharmacol. 1994 Sep;350(3):267-76 PubMed
Br J Pharmacol. 2009 Apr;156(7):1147-53 PubMed
Circulation. 1996 Sep 1;94(5):1109-17 PubMed
Br J Pharmacol. 2009 Nov;158(6):1557-64 PubMed
Br J Pharmacol. 2008 Feb;153(4):684-92 PubMed
Br J Pharmacol. 2005 Aug;145(8):1153-9 PubMed
Endocr Regul. 2010 Apr;44(2):69-75 PubMed
Life Sci. 2001 Apr 27;68(22-23):2473-9 PubMed
J Pharmacol Exp Ther. 2000 Mar;292(3):877-85 PubMed
Auton Autacoid Pharmacol. 2007 Jan;27(1):1-11 PubMed
Physiol Res. 2010;59(5):679-689 PubMed
Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H810-20 PubMed
Cell Mol Neurobiol. 2012 Jul;32(5):859-69 PubMed
Naunyn Schmiedebergs Arch Pharmacol. 2003 Oct;368(4):316-9 PubMed
Life Sci. 1996 May 24;58(26):2423-30 PubMed
J Mol Cell Cardiol. 2005 May;38(5):703-14 PubMed
Neuroreport. 1996 Jan 31;7(2):417-20 PubMed
J Biol Chem. 1993 Apr 15;268(11):7949-57 PubMed
Br J Pharmacol. 2004 Jun;142(3):395-408 PubMed
Auton Neurosci. 2009 Oct 5;150(1-2):8-20 PubMed
FASEB J. 2004 Apr;18(6):711-3 PubMed
Circ Res. 1984 Jun;54(6):703-10 PubMed
Int J Cardiol. 2011 May 5;148(3):331-6 PubMed
Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1692-7 PubMed
Chronobiol Int. 2006;23(4):795-812 PubMed
Biochem J. 2003 Sep 1;374(Pt 2):281-96 PubMed
Naunyn Schmiedebergs Arch Pharmacol. 2007 Oct;376(1-2):83-92 PubMed
Am J Physiol Regul Integr Comp Physiol. 2002 May;282(5):R1356-63 PubMed
Life Sci. 2001 Apr 27;68(22-23):2457-66 PubMed
Am J Physiol Heart Circ Physiol. 2008 Apr;294(4):H1581-8 PubMed
Life Sci. 1998;63(13):1169-82 PubMed
Pflugers Arch. 2003 Nov;447(2):254-8 PubMed
Annu Rev Pharmacol Toxicol. 2009;49:1-30 PubMed
Eur J Pharmacol. 2006 Mar 8;533(1-3):57-68 PubMed
Recept Channels. 2003;9(4):279-90 PubMed
J Pharmacol Exp Ther. 2009 Aug;330(2):487-93 PubMed
J Biol Chem. 1999 Jun 11;274(24):16694-700 PubMed
Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H192-9 PubMed
J Neuroendocrinol. 2005 Dec;17(12):817-26 PubMed
J Pharmacol Exp Ther. 2009 Jun;329(3):1156-65 PubMed
Eur J Pharmacol. 2004 Oct 1;500(1-3):167-76 PubMed
J Biol Chem. 2005 Apr 8;280(14):13624-30 PubMed
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7375-80 PubMed
Naunyn Schmiedebergs Arch Pharmacol. 2008 Jul;378(1):103-16 PubMed
Naunyn Schmiedebergs Arch Pharmacol. 2002 Feb;365(2):112-22 PubMed
Pharmacol Ther. 2008 Jan;117(1):1-29 PubMed
