Chrm2

Summary

Gene Symbol: Chrm2
Description: cholinergic receptor, muscarinic 2, cardiac
Alias: AChR-M2, Chrm-2, muscarinic acetylcholine receptor M2, AChR M2, muscarinic acetylcholine receptor 2
Species: mouse
Products:     Chrm2

Top Publications

  1. Hemrick Luecke S, Bymaster F, Evans D, Wess J, Felder C. Muscarinic agonist-mediated increases in serum corticosterone levels are abolished in m(2) muscarinic acetylcholine receptor knockout mice. J Pharmacol Exp Ther. 2002;303:99-103 pubmed
    ..These data suggest that the muscarinic M(2) receptor subtype mediates muscarinic agonist-induced activation of the hypothalamic-pituitary-adrenocortical axis in mice. ..
  2. Duttaroy A, Gomeza J, Gan J, Siddiqui N, Basile A, Harman W, et al. Evaluation of muscarinic agonist-induced analgesia in muscarinic acetylcholine receptor knockout mice. Mol Pharmacol. 2002;62:1084-93 pubmed
    ..These findings should be of considerable relevance for the development of receptor subtype-selective muscarinic agonists as novel analgesic drugs. ..
  3. Zimring J, Kapp L, Yamada M, Wess J, Kapp J. Regulation of CD8+ cytolytic T lymphocyte differentiation by a cholinergic pathway. J Neuroimmunol. 2005;164:66-75 pubmed
    ..Together, these findings suggest that the M1 muscarinic receptor is involved in CTL development, thus providing novel insights into CD8+ T cell biology and the potential role of cholinergic signaling in immune regulation. ..
  4. Xie G, Drachenberg C, Yamada M, Wess J, Raufman J. Cholinergic agonist-induced pepsinogen secretion from murine gastric chief cells is mediated by M1 and M3 muscarinic receptors. Am J Physiol Gastrointest Liver Physiol. 2005;289:G521-9 pubmed
    ..The development of a murine secretory model facilitates use of transgenic mice to investigate the regulation of pepsinogen secretion...
  5. LaCroix C, Freeling J, Giles A, Wess J, Li Y. Deficiency of M2 muscarinic acetylcholine receptors increases susceptibility of ventricular function to chronic adrenergic stress. Am J Physiol Heart Circ Physiol. 2008;294:H810-20 pubmed
    ..The overall results from this study suggest that M(2)-AChR-mediated PSNS function may provide cardiac protection. Lack of this protective mechanism will increase the susceptibility of the heart to cardiac stresses. ..
  6. Tzavara E, Bymaster F, Felder C, Wade M, Gomeza J, Wess J, et al. Dysregulated hippocampal acetylcholine neurotransmission and impaired cognition in M2, M4 and M2/M4 muscarinic receptor knockout mice. Mol Psychiatry. 2003;8:673-9 pubmed
    ..Together these results suggest a crucial role for muscarinic M2 and M4 receptors in the tonic and phasic regulation of acetylcholine efflux in the hippocampus as well as in cognitive processes. ..
  7. Unno T, Matsuyama H, Sakamoto T, Uchiyama M, Izumi Y, Okamoto H, et al. M(2) and M(3) muscarinic receptor-mediated contractions in longitudinal smooth muscle of the ileum studied with receptor knockout mice. Br J Pharmacol. 2005;146:98-108 pubmed
    ..In intact tissues coexpressing M(2) and M(3) receptors, M(2) receptor activity appears functionally relevant only when fractional receptor occupation is relatively small. ..
  8. Zhang W, Yamada M, Gomeza J, Basile A, Wess J. Multiple muscarinic acetylcholine receptor subtypes modulate striatal dopamine release, as studied with M1-M5 muscarinic receptor knock-out mice. J Neurosci. 2002;22:6347-52 pubmed
    ..These findings should contribute to a better understanding of the important functional roles that the muscarinic cholinergic system plays in striatal function. ..
  9. Matsui M, Motomura D, Fujikawa T, Jiang J, Takahashi S, Manabe T, et al. Mice lacking M2 and M3 muscarinic acetylcholine receptors are devoid of cholinergic smooth muscle contractions but still viable. J Neurosci. 2002;22:10627-32 pubmed
    ..These results collectively suggest that an additional mechanism operates in the control of pupillary constriction-dilatation...
  10. Sakamoto T, Unno T, Kitazawa T, Taneike T, Yamada M, Wess J, et al. Three distinct muscarinic signalling pathways for cationic channel activation in mouse gut smooth muscle cells. J Physiol. 2007;582:41-61 pubmed
    ..The delineation of this pathway is consistent with the formation of a functional unit by the M2-Go protein and the M3-PLC systems predicted to control cationic channels. ..

Detail Information

Publications90

  1. Hemrick Luecke S, Bymaster F, Evans D, Wess J, Felder C. Muscarinic agonist-mediated increases in serum corticosterone levels are abolished in m(2) muscarinic acetylcholine receptor knockout mice. J Pharmacol Exp Ther. 2002;303:99-103 pubmed
    ..These data suggest that the muscarinic M(2) receptor subtype mediates muscarinic agonist-induced activation of the hypothalamic-pituitary-adrenocortical axis in mice. ..
  2. Duttaroy A, Gomeza J, Gan J, Siddiqui N, Basile A, Harman W, et al. Evaluation of muscarinic agonist-induced analgesia in muscarinic acetylcholine receptor knockout mice. Mol Pharmacol. 2002;62:1084-93 pubmed
    ..These findings should be of considerable relevance for the development of receptor subtype-selective muscarinic agonists as novel analgesic drugs. ..
  3. Zimring J, Kapp L, Yamada M, Wess J, Kapp J. Regulation of CD8+ cytolytic T lymphocyte differentiation by a cholinergic pathway. J Neuroimmunol. 2005;164:66-75 pubmed
    ..Together, these findings suggest that the M1 muscarinic receptor is involved in CTL development, thus providing novel insights into CD8+ T cell biology and the potential role of cholinergic signaling in immune regulation. ..
  4. Xie G, Drachenberg C, Yamada M, Wess J, Raufman J. Cholinergic agonist-induced pepsinogen secretion from murine gastric chief cells is mediated by M1 and M3 muscarinic receptors. Am J Physiol Gastrointest Liver Physiol. 2005;289:G521-9 pubmed
    ..The development of a murine secretory model facilitates use of transgenic mice to investigate the regulation of pepsinogen secretion...
  5. LaCroix C, Freeling J, Giles A, Wess J, Li Y. Deficiency of M2 muscarinic acetylcholine receptors increases susceptibility of ventricular function to chronic adrenergic stress. Am J Physiol Heart Circ Physiol. 2008;294:H810-20 pubmed
    ..The overall results from this study suggest that M(2)-AChR-mediated PSNS function may provide cardiac protection. Lack of this protective mechanism will increase the susceptibility of the heart to cardiac stresses. ..
  6. Tzavara E, Bymaster F, Felder C, Wade M, Gomeza J, Wess J, et al. Dysregulated hippocampal acetylcholine neurotransmission and impaired cognition in M2, M4 and M2/M4 muscarinic receptor knockout mice. Mol Psychiatry. 2003;8:673-9 pubmed
    ..Together these results suggest a crucial role for muscarinic M2 and M4 receptors in the tonic and phasic regulation of acetylcholine efflux in the hippocampus as well as in cognitive processes. ..
  7. Unno T, Matsuyama H, Sakamoto T, Uchiyama M, Izumi Y, Okamoto H, et al. M(2) and M(3) muscarinic receptor-mediated contractions in longitudinal smooth muscle of the ileum studied with receptor knockout mice. Br J Pharmacol. 2005;146:98-108 pubmed
    ..In intact tissues coexpressing M(2) and M(3) receptors, M(2) receptor activity appears functionally relevant only when fractional receptor occupation is relatively small. ..
  8. Zhang W, Yamada M, Gomeza J, Basile A, Wess J. Multiple muscarinic acetylcholine receptor subtypes modulate striatal dopamine release, as studied with M1-M5 muscarinic receptor knock-out mice. J Neurosci. 2002;22:6347-52 pubmed
    ..These findings should contribute to a better understanding of the important functional roles that the muscarinic cholinergic system plays in striatal function. ..
  9. Matsui M, Motomura D, Fujikawa T, Jiang J, Takahashi S, Manabe T, et al. Mice lacking M2 and M3 muscarinic acetylcholine receptors are devoid of cholinergic smooth muscle contractions but still viable. J Neurosci. 2002;22:10627-32 pubmed
    ..These results collectively suggest that an additional mechanism operates in the control of pupillary constriction-dilatation...
  10. Sakamoto T, Unno T, Kitazawa T, Taneike T, Yamada M, Wess J, et al. Three distinct muscarinic signalling pathways for cationic channel activation in mouse gut smooth muscle cells. J Physiol. 2007;582:41-61 pubmed
    ..The delineation of this pathway is consistent with the formation of a functional unit by the M2-Go protein and the M3-PLC systems predicted to control cationic channels. ..
  11. Slutsky I, Wess J, Gomeza J, Dudel J, Parnas I, Parnas H. Use of knockout mice reveals involvement of M2-muscarinic receptors in control of the kinetics of acetylcholine release. J Neurophysiol. 2003;89:1954-67 pubmed
    ..These results support our earlier findings and provide direct evidence for the major role that presynaptic M(2)-muscarinic receptors play in the control of the time course of evoked acetylcholine release under physiological conditions. ..
  12. Gomeza J, Shannon H, Kostenis E, Felder C, Zhang L, Brodkin J, et al. Pronounced pharmacologic deficits in M2 muscarinic acetylcholine receptor knockout mice. Proc Natl Acad Sci U S A. 1999;96:1692-7 pubmed
    ..These results offer a rational basis for the development of novel muscarinic drugs. ..
  13. Stengel P, Gomeza J, Wess J, Cohen M. M(2) and M(4) receptor knockout mice: muscarinic receptor function in cardiac and smooth muscle in vitro. J Pharmacol Exp Ther. 2000;292:877-85 pubmed
  14. Nobles M, Sebastian S, Tinker A. HL-1 cells express an inwardly rectifying K+ current activated via muscarinic receptors comparable to that in mouse atrial myocytes. Pflugers Arch. 2010;460:99-108 pubmed publisher
    ..Real-time RT-PCR confirms the presence of mRNA for the main G-protein subunits, as well as for M2 muscarinic and A1 adenosine receptors. The data suggest HL-1 cells are a good model to study IKAch. ..
  15. Kupchik Y, Rashkovan G, Ohana L, Keren Raifman T, Dascal N, Parnas H, et al. Molecular mechanisms that control initiation and termination of physiological depolarization-evoked transmitter release. Proc Natl Acad Sci U S A. 2008;105:4435-40 pubmed publisher
    ..The free machinery, together with Ca(2+) that had already entered, initiates release. Release terminates when the reverse occurs upon repolarization. ..
  16. Kistemaker L, Bos S, Mudde W, Hylkema M, Hiemstra P, Wess J, et al. Muscarinic M? receptors contribute to allergen-induced airway remodeling in mice. Am J Respir Cell Mol Biol. 2014;50:690-8 pubmed publisher
    ..No stimulatory role for muscarinic M3 receptors in allergic inflammation was observed, suggesting that the role of acetylcholine in remodeling is independent of the allergic inflammatory response, and may involve bronchoconstriction. ..
  17. Kistemaker L, Bos I, Hylkema M, Nawijn M, Hiemstra P, Wess J, et al. Muscarinic receptor subtype-specific effects on cigarette smoke-induced inflammation in mice. Eur Respir J. 2013;42:1677-88 pubmed publisher
    ..Collectively, our data indicate a pro-inflammatory role for the M3 receptor in cigarette smoke-induced neutrophilia and cytokine release, yet an anti-inflammatory role for M1 and M2 receptors. ..
  18. Stirnweiss J, Valkova C, Ziesché E, Drube S, Liebmann C. Muscarinic M2 receptors mediate transactivation of EGF receptor through Fyn kinase and without matrix metalloproteases. Cell Signal. 2006;18:1338-49 pubmed
    ..This specific role of Fyn can be verified in SH-SY5Y human neuroblastoma cells with endogenously expressed M2 receptors. ..
  19. Ruggieri M, Braverman A. Gastric body cholinergic contractile signal transduction in M2 and M3 receptor knockout mice. J Recept Signal Transduct Res. 2013;33:249-54 pubmed publisher
    ..These studies suggest that multiple parallel pathways mediate cholinergic contractions in stomach body smooth muscle. ..
  20. Nenasheva T, Neary M, Mashanov G, Birdsall N, Breckenridge R, Molloy J. Abundance, distribution, mobility and oligomeric state of M? muscarinic acetylcholine receptors in live cardiac muscle. J Mol Cell Cardiol. 2013;57:129-36 pubmed publisher
    ..Our estimated encounter rate of 5-10 collisions per second, may explain the latency between acetylcholine application and GIRK channel opening...
  21. Degroot A, Salhoff C, Davis R, Nomikos G. Genetic deletion of CB1 receptors improves non-associative learning. Behav Brain Res. 2005;162:161-4 pubmed
    ..We conclude that CB1 receptor gene invalidation improves habituation tentatively through an increase in cholinergic neurotransmission. ..
  22. Nadal L, Garcia N, Hurtado E, Simó A, Tomas M, Lanuza M, et al. Presynaptic muscarinic acetylcholine autoreceptors (M1, M2 and M4 subtypes), adenosine receptors (A1 and A2A) and tropomyosin-related kinase B receptor (TrkB) modulate the developmental synapse elimination process at the neuromuscular junction. Mol Brain. 2016;9:67 pubmed publisher
  23. Liu J, Rasul I, Sun Y, Wu G, Li L, Premont R, et al. GRK5 deficiency leads to reduced hippocampal acetylcholine level via impaired presynaptic M2/M4 autoreceptor desensitization. J Biol Chem. 2009;284:19564-71 pubmed publisher
  24. Dasari S, Gulledge A. M1 and M4 receptors modulate hippocampal pyramidal neurons. J Neurophysiol. 2011;105:779-92 pubmed publisher
    ..We therefore conclude that M1 and M4 receptors are the major mAChR subtypes responsible for direct cholinergic modulation of the excitatory hippocampal circuit. ..
  25. Maison S, Liu X, Vetter D, Eatock R, Nathanson N, Wess J, et al. Muscarinic signaling in the cochlea: presynaptic and postsynaptic effects on efferent feedback and afferent excitability. J Neurosci. 2010;30:6751-62 pubmed publisher
  26. Kupchik Y, Barchad Avitzur O, Wess J, Ben Chaim Y, Parnas I, Parnas H. A novel fast mechanism for GPCR-mediated signal transduction--control of neurotransmitter release. J Cell Biol. 2011;192:137-51 pubmed publisher
    ..Our results suggest that, in addition to Ca(2+) influx, charge movement in GPCRs is also necessary for release control...
  27. Lammerding Koppel M, Greiner Schröder A, Drews U. Muscarinic receptors in the prenatal mouse embryo. Comparison of M35-immunohistochemistry with [3H]quinuclidinyl benzylate autoradiography. Histochem Cell Biol. 1995;103:301-10 pubmed
    ..A large amount of embryonic muscarinic receptors was found in the remnants of the notochord and in the nucleus pulposus of the developing vertebral column. A function in morphogenesis is discussed of the embryonic muscarinic receptor. ..
  28. Lamping K, Wess J, Cui Y, Nuno D, Faraci F. Muscarinic (M) receptors in coronary circulation: gene-targeted mice define the role of M2 and M3 receptors in response to acetylcholine. Arterioscler Thromb Vasc Biol. 2004;24:1253-8 pubmed
    ..Similar results were obtained in aorta rings. These findings provide the first direct evidence that relaxation to ACh in coronary circulation is mediated predominantly by activation of M3 receptors. ..
  29. Semenov I, Wang B, Herlihy J, Brenner R. BK channel ?1 subunits regulate airway contraction secondary to M2 muscarinic acetylcholine receptor mediated depolarization. J Physiol. 2011;589:1803-17 pubmed publisher
  30. Shapiro M, Loose M, Hamilton S, Nathanson N, Gomeza J, Wess J, et al. Assignment of muscarinic receptor subtypes mediating G-protein modulation of Ca(2+) channels by using knockout mice. Proc Natl Acad Sci U S A. 1999;96:10899-904 pubmed
    ..The knockout effects are clean and are apparently not accompanied by compensatory changes in other muscarinic receptors. ..
  31. Gautam D, Duttaroy A, Cui Y, Han S, Deng C, Seeger T, et al. M1-M3 muscarinic acetylcholine receptor-deficient mice: novel phenotypes. J Mol Neurosci. 2006;30:157-60 pubmed
    ..This chapter summarizes recent findings dealing with the importance of the M2mAChR for cognitive processes and the roles of the M1 and M3 mAChRs in mediating stimulation of glandular secretion. ..
  32. Azuma Y, Samezawa N, Nishiyama K, Nakajima H, Takeuchi T. Differences in time to peak carbachol-induced contractions between circular and longitudinal smooth muscles of mouse ileum. Naunyn Schmiedebergs Arch Pharmacol. 2016;389:63-72 pubmed
    ..Our findings indicate that muscarinic M2 receptors in the circular muscular layer of mouse ileum exert a previously undocumented function in gut motility via the regulation of gap junctions. ..
  33. Bernard V, Brana C, Liste I, Lockridge O, Bloch B. Dramatic depletion of cell surface m2 muscarinic receptor due to limited delivery from intracytoplasmic stores in neurons of acetylcholinesterase-deficient mice. Mol Cell Neurosci. 2003;23:121-33 pubmed
  34. Zhang H, Chen S, Matsui M, Gautam D, Wess J, Pan H. Opposing functions of spinal M2, M3, and M4 receptor subtypes in regulation of GABAergic inputs to dorsal horn neurons revealed by muscarinic receptor knockout mice. Mol Pharmacol. 2006;69:1048-55 pubmed
    ..In contrast, stimulation of presynaptic M2 and M4 subtypes predominantly attenuates GABAergic inputs to dorsal horn neurons in mice, an action that is opposite to the role of M2 and M4 subtypes in the spinal cord of rats. ..
  35. Takeuchi T, Tanaka K, Nakajima H, Matsui M, Azuma Y. M2 and M3 muscarinic receptors are involved in enteric nerve-mediated contraction of the mouse ileum: Findings obtained with muscarinic-receptor knockout mouse. Am J Physiol Gastrointest Liver Physiol. 2007;292:G154-64 pubmed
    ..These results suggest that atropine-sensitive phasic contraction is mainly mediated via the M3 receptor, and SP-mediated sustained contraction is negatively regulated by the M2 receptor at a presynaptic level. ..
  36. Douglas C, Baghdoyan H, Lydic R. Prefrontal cortex acetylcholine release, EEG slow waves, and spindles are modulated by M2 autoreceptors in C57BL/6J mouse. J Neurophysiol. 2002;87:2817-22 pubmed
    ..EEG slow-wave activity varies across mouse strains, and the results encourage comparative phenotyping of cortical ACh release and EEG in additional mouse models...
  37. Boyer S, Clancy S, Terunuma M, Revilla Sanchez R, Thomas S, Moss S, et al. Direct interaction of GABAB receptors with M2 muscarinic receptors enhances muscarinic signaling. J Neurosci. 2009;29:15796-809 pubmed publisher
    ..This novel heteromeric association between M(2)R and GBR2 provides a possible mechanism for altering muscarinic signaling in the brain and represents a previously unrecognized role for GBR2. ..
  38. Zhang W, Basile A, Gomeza J, Volpicelli L, Levey A, Wess J. Characterization of central inhibitory muscarinic autoreceptors by the use of muscarinic acetylcholine receptor knock-out mice. J Neurosci. 2002;22:1709-17 pubmed
    ..These results, together with additional receptor localization studies, support the novel concept that autoinhibition of ACh release involves different mAChRs in different regions of the brain. ..
  39. Rhodes M, Rubin R, McKlveen J, Karwoski T, Fulton B, Czambel R. Pituitary-adrenal responses to oxotremorine and acute stress in male and female M1 muscarinic receptor knockout mice: comparisons to M2 muscarinic receptor knockout mice. J Neuroendocrinol. 2008;20:617-25 pubmed publisher
    ..Conversely, the increased pituitary-adrenal sensitivity to these challenges noted in M(2) knockout mice is consistent with M(2) being primarily a presynaptic autoreceptor. ..
  40. Klein M, Haberberger R, Hartmann P, Faulhammer P, Lips K, Krain B, et al. Muscarinic receptor subtypes in cilia-driven transport and airway epithelial development. Eur Respir J. 2009;33:1113-21 pubmed publisher
    ..The M1 receptor increases cilia-driven particle transport if the M3 and M2 receptors are missing. None of the receptors is necessary for epithelial development. ..
  41. Bymaster F, McKinzie D, Felder C, Wess J. Use of M1-M5 muscarinic receptor knockout mice as novel tools to delineate the physiological roles of the muscarinic cholinergic system. Neurochem Res. 2003;28:437-42 pubmed
    ..M4 mAChRs modulate dopamine activity in motor tracts and act as inhibitory autoreceptors in striatum. Thus, as elucidated by gene targeting technology, mAChRs have widespread and manifold functions in the periphery and brain. ..
  42. Unno T, Matsuyama H, Izumi Y, Yamada M, Wess J, Komori S. Roles of M2 and M3 muscarinic receptors in cholinergic nerve-induced contractions in mouse ileum studied with receptor knockout mice. Br J Pharmacol. 2006;149:1022-30 pubmed
    ..Our data also suggest that the lack of both M(2) and M(3) receptors causes upregulation of noncholinergic excitatory innervation of the gut smooth muscle. ..
  43. Chen S, Chen H, Yuan W, Wess J, Pan H. Differential regulation of primary afferent input to spinal cord by muscarinic receptor subtypes delineated using knockout mice. J Biol Chem. 2014;289:14321-30 pubmed publisher
    ..Activation of the M5 subtype either directly increases primary afferent input or inhibits it through indirectly stimulating group II/III mGluRs. ..
  44. Ehrhardt A, Wang B, Yung A, Wang Y, Kozlowski P, van Breemen C, et al. Urinary Retention, Incontinence, and Dysregulation of Muscarinic Receptors in Male Mice Lacking Mras. PLoS ONE. 2015;10:e0141493 pubmed publisher
    ..Our observations also support the notion that bladder control is sexually dimorphic and is regulated through mechanisms that are largely independent of acetylcholine signaling in female mice. ..
  45. Shin J, Adrover M, Wess J, Alvarez V. Muscarinic regulation of dopamine and glutamate transmission in the nucleus accumbens. Proc Natl Acad Sci U S A. 2015;112:8124-9 pubmed publisher
    ..Our findings clarify the mechanisms of mAChR-dependent modulation of DA and glutamate transmission in the striatum. ..
  46. Takeuchi T, Fujinami K, Goto H, Fujita A, Taketo M, Manabe T, et al. Roles of M2 and M4 muscarinic receptors in regulating acetylcholine release from myenteric neurons of mouse ileum. J Neurophysiol. 2005;93:2841-8 pubmed
    ..M1, M3, and M5 receptors do not seem to be involved in this mechanism. ..
  47. Joseph L, Thomsen M. Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor M1, M2, and M4 receptor knockout mice. Behav Brain Res. 2017;329:75-83 pubmed publisher
  48. Zhang H, Zhou H, Chen S, Gautam D, Wess J, Pan H. Control of glycinergic input to spinal dorsal horn neurons by distinct muscarinic receptor subtypes revealed using knockout mice. J Pharmacol Exp Ther. 2007;323:963-71 pubmed
    ..This study revealed distinct functions of mAChR subtypes in controlling glycinergic input to spinal dorsal horn neurons. ..
  49. Hubsch M, Neuhuber W, Raab M. Muscarinic acetylcholine receptors in the mouse esophagus: focus on intraganglionic laminar endings (IGLEs). Neurogastroenterol Motil. 2013;25:e560-73 pubmed publisher
    ..Acetylcholine probably released from varicosities of both extrinsic and intrinsic origin may influence a subpopulation of esophageal IGLEs via M2 and M1-receptors. ..
  50. Porter G, Rivkees S. Ontogeny of humoral heart rate regulation in the embryonic mouse. Am J Physiol Regul Integr Comp Physiol. 2001;281:R401-7 pubmed
    ..0. These results identify the adenosinergic system as the earliest and most potent regulator of embryonic cardiac function and show that prenatal responsiveness to catecholamines and acetylcholine develops at later embryonic stages...
  51. Zheng F, Wess J, Alzheimer C. M2 muscarinic acetylcholine receptors regulate long-term potentiation at hippocampal CA3 pyramidal cell synapses in an input-specific fashion. J Neurophysiol. 2012;108:91-100 pubmed publisher
    ..Our data demonstrate that cholinergic projections recruit M(2) receptors to redistribute the gain of LTP in CA3 pyramidal cells in an input-specific manner. ..
  52. Seeger T, Fedorova I, Zheng F, Miyakawa T, Koustova E, Gomeza J, et al. M2 muscarinic acetylcholine receptor knock-out mice show deficits in behavioral flexibility, working memory, and hippocampal plasticity. J Neurosci. 2004;24:10117-27 pubmed
    ..Because impaired muscarinic cholinergic neurotransmission is associated with Alzheimer's disease and normal aging processes, these findings should be of considerable therapeutic relevance. ..
  53. Shi Y, Oury F, Yadav V, Wess J, Liu X, Guo X, et al. Signaling through the M(3) muscarinic receptor favors bone mass accrual by decreasing sympathetic activity. Cell Metab. 2010;11:231-8 pubmed publisher
    ..By showing that both arms of the autonomic nervous system affect bone remodeling, this study further underscores the importance of neuronal regulation of bone. ..
  54. Kashihara T, Hirose M, Shimojo H, Nakada T, Gomi S, Hongo M, et al. ?(2)-Adrenergic and M(2)-muscarinic receptors decrease basal t-tubular L-type Ca2+ channel activity and suppress ventricular contractility in heart failure. Eur J Pharmacol. 2014;724:122-31 pubmed publisher
    ..Therefore, antagonists of ?2-adrenergic and/or M2-muscarinic receptors can be good adjuncts to ?1-adrenergic receptor antagonists in the treatment of heart failure. ..
  55. Zhou X, Wulfsen I, Lutz S, Utku E, Sausbier U, Ruth P, et al. M2 muscarinic receptors induce airway smooth muscle activation via a dual, Gbetagamma-mediated inhibition of large conductance Ca2+-activated K+ channel activity. J Biol Chem. 2008;283:21036-44 pubmed publisher
    ..Our results demonstrate that airway M(2)Rs inhibit BK channels by a dual, Gbetagamma-mediated mechanism, a direct membrane-delimited interaction, and the activation of the phospholipase C/protein kinase C pathway. ..
  56. Arteaga Solis E, Zee T, Emala C, Vinson C, Wess J, Karsenty G. Inhibition of leptin regulation of parasympathetic signaling as a cause of extreme body weight-associated asthma. Cell Metab. 2013;17:35-48 pubmed publisher
    ..These findings may be of use in the management of obesity-associated asthma. ..
  57. Bernardini N, Roza C, Sauer S, Gomeza J, Wess J, Reeh P. Muscarinic M2 receptors on peripheral nerve endings: a molecular target of antinociception. J Neurosci. 2002;22:RC229 pubmed
    ..This observation should be of interest for the development of novel classes of analgesic agents. ..
  58. Yoshizawa A, Nagai S, Baba Y, Yamada T, Matsui M, Tanaka H, et al. Autoimmunity against M?muscarinic acetylcholine receptor induces myocarditis and leads to a dilated cardiomyopathy-like phenotype. Eur J Immunol. 2012;42:1152-63 pubmed publisher
    ..Our mouse model will be useful in the analysis of the molecular mechanisms of disease progression and the development of new therapies for DCM. ..
  59. Kuczewski N, Aztiria E, Gautam D, Wess J, Domenici L. Acetylcholine modulates cortical synaptic transmission via different muscarinic receptors, as studied with receptor knockout mice. J Physiol. 2005;566:907-19 pubmed
    ..The present data suggest that local ACh, acting through mAChRs, regulates the cortical dynamics making cortical circuits respond to specific stimuli. ..
  60. d Alcantara P, Ledent C, Swillens S, Schiffmann S. Inactivation of adenosine A2A receptor impairs long term potentiation in the accumbens nucleus without altering basal synaptic transmission. Neuroscience. 2001;107:455-64 pubmed
  61. Schlenz H, Kummer W, Jositsch G, Wess J, Krasteva G. Muscarinic receptor-mediated bronchoconstriction is coupled to caveolae in murine airways. Am J Physiol Lung Cell Mol Physiol. 2010;298:L626-36 pubmed publisher
    ..Here, we demonstrated that M2R- and M3R-mediated bronchoconstriction is caveolae-dependent. Since caveolin-3 is directly associated with M2R, we suggest caveolin-3 as novel regulator of M2R-mediated signaling. ..
  62. Decossas M, Bloch B, Bernard V. Trafficking of the muscarinic m2 autoreceptor in cholinergic basalocortical neurons in vivo: differential regulation of plasma membrane receptor availability and intraneuronal localization in acetylcholinesterase-deficient and -inhibited mice. J Comp Neurol. 2003;462:302-14 pubmed
    ..The increase of m2R at the membrane of axonal varicosities after chronic stimulation suggest modulation of presynaptic cholinergic activity, including neurotransmitter release. ..
  63. Gao X, Zhao Y, Su Y, Liu K, Yu X, Cui C, et al. ?1/2 or M2/3 Receptors Are Required for Different Gastrointestinal Motility Responses Induced by Acupuncture at Heterotopic or Homotopic Acupoints. PLoS ONE. 2016;11:e0168200 pubmed publisher
    ..Therefore, our findings reveal important biological mechanisms underlying acupuncture treatment of disorders involving gastrointestinal motility dysfunction. ..
  64. Gămănuţ R, Kennedy H, Toroczkai Z, Ercsey Ravasz M, Van Essen D, Knoblauch K, et al. The Mouse Cortical Connectome, Characterized by an Ultra-Dense Cortical Graph, Maintains Specificity by Distinct Connectivity Profiles. Neuron. 2018;97:698-715.e10 pubmed publisher
    ..The consistency, precision of the connectivity profile, density, and weighted graph analysis of the present data differ significantly from those obtained in earlier studies in the mouse. ..
  65. Cymes G, Grosman C, Auerbach A. Structure of the transition state of gating in the acetylcholine receptor channel pore: a phi-value analysis. Biochemistry. 2002;41:5548-55 pubmed
    ..We also elaborate on unsettled aspects of the analysis such as the accuracy of two-point LFERs, the physical interpretation of fractional Phi-values, and the existence of single versus parallel transition states for the gating reaction. ..
  66. Bymaster F, Carter P, Yamada M, Gomeza J, Wess J, Hamilton S, et al. Role of specific muscarinic receptor subtypes in cholinergic parasympathomimetic responses, in vivo phosphoinositide hydrolysis, and pilocarpine-induced seizure activity. Eur J Neurosci. 2003;17:1403-10 pubmed
    ..Muscarinic M1 receptors appear to be the only muscarinic receptor subtype mediating seizures. ..
  67. Hamada S, Houtani T, Trifonov S, Kase M, Maruyama M, Shimizu J, et al. Histological determination of the areas enriched in cholinergic terminals and M2 and M3 muscarinic receptors in the mouse central auditory system. Anat Rec (Hoboken). 2010;293:1393-9 pubmed publisher
  68. Fisher J, Vincent S, Gomeza J, Yamada M, Wess J. Loss of vagally mediated bradycardia and bronchoconstriction in mice lacking M2 or M3 muscarinic acetylcholine receptors. FASEB J. 2004;18:711-3 pubmed
  69. Degroot A, Nomikos G. Genetic deletion of muscarinic M4 receptors is anxiolytic in the shock-probe burying model. Eur J Pharmacol. 2006;531:183-6 pubmed
    ..Therefore, muscarinic M4 receptors are of particular significance in anxiety modulation that seems dissociated from changes in long-term memory. ..
  70. Rhodes M, Billings T, Czambel R, Rubin R. Pituitary-adrenal responses to cholinergic stimulation and acute mild stress are differentially elevated in male and female M(2) muscarinic receptor knockout mice. J Neuroendocrinol. 2005;17:817-26 pubmed
    ..Because ACTH and corticosterone responses were greater in male and female M(2) KO mice, the M(2) receptor appears to dampen the stress response. ..
  71. Mohr F, Krejci E, Zimmermann M, Klein J. Dysfunctional Presynaptic M2 Receptors in the Presence of Chronically High Acetylcholine Levels: Data from the PRiMA Knockout Mouse. PLoS ONE. 2015;10:e0141136 pubmed publisher
    ..Remarkably, this loss of function does not affect cognitive functions in PRiMA knockout mice. Our results are discussed in the context of AChE inhibitor therapy as used in dementia. ..
  72. Zarghooni S, Wunsch J, Bodenbenner M, Brüggmann D, Grando S, Schwantes U, et al. Expression of muscarinic and nicotinic acetylcholine receptors in the mouse urothelium. Life Sci. 2007;80:2308-13 pubmed
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    ..These results demonstrate that M(2)/M(4) muscarinic autoreceptors regulate ACh release from striatal ChIs. As a consequence, endogenous ACh drives the polarity of bidirectional synaptic plasticity. ..
  74. Rocha N, Garcia S, Giménez L, Hernández C, Senra J, Lima R, et al. Characterization of cardiopulmonary function and cardiac muscarinic and adrenergic receptor density adaptation in C57BL/6 mice with chronic Trypanosoma cruzi infection. Parasitology. 2006;133:729-37 pubmed
  75. Liu Q, Zheng Y, Korde A, Yadav V, Rathore R, Wess J, et al. Membrane depolarization causes a direct activation of G protein-coupled receptors leading to local Ca2+ release in smooth muscle. Proc Natl Acad Sci U S A. 2009;106:11418-23 pubmed publisher
    ..These findings demonstrate an important mechanism for Ca(2+) signaling and attendant physiological function in SMCs. ..
  76. Chen S, Chen H, Yuan W, Wess J, Pan H. Dynamic control of glutamatergic synaptic input in the spinal cord by muscarinic receptor subtypes defined using knockout mice. J Biol Chem. 2010;285:40427-37 pubmed publisher
    ..M(5) is the predominant receptor subtype that potentiates glutamatergic synaptic transmission in the spinal cord. ..
  77. Nichols J, Gladwell W, Verhein K, Cho H, Wess J, Suzuki O, et al. Genome-wide association mapping of acute lung injury in neonatal inbred mice. FASEB J. 2014;28:2538-50 pubmed publisher
    ..Comparative mapping of the chromosome 6 QTLs identified Chrm2 (cholinergic receptor, muscarinic 2, cardiac) as a candidate susceptibility gene, and mouse strains with a ..
  78. Shapiro R, Scherer N, Habecker B, Subers E, Nathanson N. Isolation, sequence, and functional expression of the mouse M1 muscarinic acetylcholine receptor gene. J Biol Chem. 1988;263:18397-403 pubmed
    ..In addition, these results indicate that different subtypes of the muscarinic receptor are coupled to different physiological responses. ..
  79. Manuel I, Lombardero L, LaFerla F, Gimenez Llort L, Rodriguez Puertas R. Activity of muscarinic, galanin and cannabinoid receptors in the prodromal and advanced stages in the triple transgenic mice model of Alzheimer's disease. Neuroscience. 2016;329:284-93 pubmed publisher
    ..The up-regulation of galaninergic and endocannabinoid systems support the hypothesis of their neuroprotective roles, and these are established prior to the onset of clear clinical cognitive symptoms of the disease. ..
  80. Boudinot E, Champagnat J, Foutz A. M(1)/M(3) and M(2)/M(4) muscarinic receptor double-knockout mice present distinct respiratory phenotypes. Respir Physiol Neurobiol. 2008;161:54-61 pubmed publisher
    ..The results suggest that M(1) and M(3) receptors are involved in the control of tidal volume, while M(2) and M(4) receptors may be involved in the control of breathing frequency at rest and response to stress. ..
  81. Barathi V, Kwan J, Tan Q, Weon S, Seet L, Goh L, et al. Muscarinic cholinergic receptor (M2) plays a crucial role in the development of myopia in mice. Dis Model Mech. 2013;6:1146-58 pubmed publisher
    ..Mice lacking the muscarinic cholinergic receptor gene (M2; also known as Chrm2) were less susceptible to lens-induced myopia compared with wild-type mice, which showed significantly increased ..
  82. Griffin M, Matsui M, Ostrom R, Ehlert F. The guinea pig ileum lacks the direct, high-potency, M(2)-muscarinic, contractile mechanism characteristic of the mouse ileum. Naunyn Schmiedebergs Arch Pharmacol. 2009;380:327-35 pubmed publisher
    ..The guinea pig ileum, therefore, lacks a direct, highly potent, M(2)-contractile component but may have a direct, lower potency M(2) component. ..
  83. Zagoraiou L, Akay T, Martin J, Brownstone R, Jessell T, Miles G. A cluster of cholinergic premotor interneurons modulates mouse locomotor activity. Neuron. 2009;64:645-62 pubmed publisher
    ..Thus, V0(C) interneurons represent a defined class of spinal cholinergic interneurons with an intrinsic neuromodulatory role in the control of locomotor behavior. ..
  84. Stengel P, Cohen M. Muscarinic receptor knockout mice: role of muscarinic acetylcholine receptors M(2), M(3), and M(4) in carbamylcholine-induced gallbladder contractility. J Pharmacol Exp Ther. 2002;301:643-50 pubmed
  85. Zhang H, Chen S, Pan H. Regulation of glutamate release from primary afferents and interneurons in the spinal cord by muscarinic receptor subtypes. J Neurophysiol. 2007;97:102-9 pubmed
    ..The M(3) and M(2)/M(4) subtypes on a subpopulation of interneurons are important for regulation of glutamate release from interneurons in the spinal dorsal horn. ..
  86. Oki T, Takagi Y, Inagaki S, Taketo M, Manabe T, Matsui M, et al. Quantitative analysis of binding parameters of [3H]N-methylscopolamine in central nervous system of muscarinic acetylcholine receptor knockout mice. Brain Res Mol Brain Res. 2005;133:6-11 pubmed
  87. Struckmann N, Schwering S, Wiegand S, Gschnell A, Yamada M, Kummer W, et al. Role of muscarinic receptor subtypes in the constriction of peripheral airways: studies on receptor-deficient mice. Mol Pharmacol. 2003;64:1444-51 pubmed
    ..Given the important role of muscarinic cholinergic mechanisms in pulmonary disease, these findings should be of considerable therapeutic relevance. ..