title: Crosstalk between beta-2-adrenoceptor and muscarinic acetylcholine receptors in the airway.
abstract: The M3 and M2 muscarinic acetylcholine receptors (mAChRs) and beta-2-adrenoceptors (β2ARs) are important regulators of airway cell function, and drugs targeting these receptors are among the first line drugs in the treatment of the obstructive lung diseases asthma and chronic obstructive lung disease (COPD). Cross-regulation or crosstalk between mAChRs and β2ARs in airway smooth muscle (ASM) helps determine the contractile state of the muscle, thus airway diameter and resistance to airflow. In this review we will detail mAChR and β2AR-signaling and crosstalk, focusing on events in the ASM cell but also addressing the function of these receptors in other cell types that impact airway physiology. We conclude by discussing how recent advances in GPCR pharmacology offer a unique opportunity to fine tune mAChR and β2AR signaling and their crosstalk, and thereby produce superior therapeutics for obstructive lung and other diseases.
authors.affiliation: Center for Translational Medicine, Jefferson-Jane and Leonard Korman Lung Center, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Tonio
authors.initials: T
authors.lastname: Pera
authors.affiliation: Center for Translational Medicine, Jefferson-Jane and Leonard Korman Lung Center, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: Raymond.Penn@jefferson.edu.
authors.forename: Raymond B
authors.initials: RB
authors.lastname: Penn
mesh_terms: D000818:Animals; D008168:Lung / Q000378:metabolism*; D043585:Receptor, Muscarinic M2 / Q000378:metabolism*; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D018343:Receptors, Adrenergic, beta-2
references.citation: J Biol Chem. 2008 Oct 24;283(43):29028-36
references.pmid: 18678875
references.citation: Eur J Pharmacol. 2008 Mar 17;582(1-3):145-53
references.pmid: 18242599
references.citation: Eur Respir J. 2010 Oct;36(4):963-5
references.pmid: 20889466
references.citation: Curr Opin Pharmacol. 2013 Jun;13(3):316-23
references.pmid: 23643733
references.citation: Chest. 2006 Mar;129(3):509-17
references.pmid: 16537846
references.citation: Eur Respir J. 2007 Oct;30(4):653-61
references.pmid: 17537779
references.citation: N Engl J Med. 2010 Oct 28;363(18):1715-26
references.pmid: 20979471
references.citation: J Cell Mol Med. 2011 Jul;15(7):1551-63
references.pmid: 20716113
references.citation: Am J Physiol. 1998 May;274(5):L803-9
references.pmid: 9612296
references.citation: Respir Res. 2003;4:2
references.pmid: 12648290
references.citation: N Engl J Med. 2011 May 26;364(21):2006-15
references.pmid: 21612469
references.citation: Am J Respir Cell Mol Biol. 2013 Jul;49(1):18-27
references.pmid: 23449734
references.citation: Am J Physiol. 1998 Jun;274(6):L970-9
references.pmid: 9609736
references.citation: Mol Pharmacol. 1999 Oct;56(4):813-23
references.pmid: 10496966
references.citation: FASEB J. 2008 Jul;22(7):2134-41
references.pmid: 18337459
references.citation: J Biol Chem. 2011 May 13;286(19):16681-92
references.pmid: 21454546
references.citation: Trends Pharmacol Sci. 2011 Sep;32(9):521-33
references.pmid: 21680031
references.citation: Mol Pharmacol. 1994 May;45(5):899-907
references.pmid: 8190106
references.citation: Am Rev Respir Dis. 1993 Feb;147(2):327-31
references.pmid: 8381630
references.citation: Br J Pharmacol. 2001 Feb;132(3):729-41
references.pmid: 11159726
references.citation: Eur Respir J. 2009 Dec;34(6):1436-43
references.pmid: 19460789
references.citation: Pulm Pharmacol Ther. 2008;21(1):134-41
references.pmid: 17703976
references.citation: N Engl J Med. 2012 Sep 27;367(13):1198-207
references.pmid: 22938706
references.citation: Am J Respir Cell Mol Biol. 2014 Apr;50(4):690-8
references.pmid: 24156289
references.citation: Am J Physiol. 1999 Sep;277(3):L653-61
references.pmid: 10484474
references.citation: J Clin Invest. 1994 Jan;93(1):371-9
references.pmid: 7904270
references.citation: Cell Health Cytoskelet. 2009 Jun 1;2009(1):27-42
references.pmid: 21686039
references.citation: Eur J Pharmacol. 2006 Jan 4;529(1-3):151-6
references.pmid: 16324695
references.citation: Thorax. 1998 Jul;53(7):613-6
references.pmid: 9797763
references.citation: Int Arch Allergy Appl Immunol. 1984;74(4):356-61
references.pmid: 6203844
references.citation: Annu Rev Pharmacol Toxicol. 2012;52:179-97
references.pmid: 21942629
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2435-40
references.pmid: 19171883
references.citation: Am J Respir Cell Mol Biol. 2003 Feb;28(2):257-62
references.pmid: 12540494
references.citation: Life Sci. 2012 Nov 27;91(21-22):1126-33
references.pmid: 22406302
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2011 Aug;384(2):133-45
references.pmid: 21603974
references.citation: FASEB J. 2004 Apr;18(6):711-3
references.pmid: 14977875
references.citation: Am J Physiol Lung Cell Mol Physiol. 2004 Feb;286(2):L312-9
references.pmid: 14565944
references.citation: Respir Med. 2012 Oct;106(10):1413-20
references.pmid: 22749044
references.citation: Eur Respir J. 2008 Sep;32(3):555-62
references.pmid: 18480105
references.citation: Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16660-5
references.pmid: 23012429
references.citation: Br J Pharmacol. 2000 Aug;130(7):1433-52
references.pmid: 10928943
references.citation: Eur J Pharmacol. 1993 Nov 9;249(2):235-8
references.pmid: 8287906
references.citation: J Clin Invest. 2003 Aug;112(4):566-74
references.pmid: 12925697
references.citation: Eur Respir J. 2011 Oct;38(4):789-96
references.pmid: 21349917
references.citation: J Biol Chem. 2012 Jun 1;287(23):18925-36
references.pmid: 22500016
references.citation: FASEB J. 2011 Jan;25(1):389-97
references.pmid: 20805374
references.citation: J Biol Chem. 2001 Aug 31;276(35):32648-56
references.pmid: 11418617
references.citation: Life Sci. 1999;64(6-7):457-64
references.pmid: 10069510
references.citation: Nature. 1997 Nov 6;390(6655):88-91
references.pmid: 9363896
references.citation: Int Arch Allergy Immunol. 2010;152(4):353-61
references.pmid: 20185927
references.citation: N Engl J Med. 1984 Aug 16;311(7):421-5
references.pmid: 6749189
references.citation: Cell Signal. 2006 Dec;18(12):2105-20
references.pmid: 16828259
references.citation: Am J Respir Cell Mol Biol. 2012 Jan;46(1):48-54
references.pmid: 22210825
references.citation: Expert Rev Respir Med. 2011 Jun;5(3):297-300
references.pmid: 21702649
references.citation: Respir Med. 2008 Jan;102(1):50-6
references.pmid: 17920256
references.citation: Am J Respir Cell Mol Biol. 2001 Jan;24(1):44-48
references.pmid: 11152649
references.citation: Mol Pharmacol. 2003 Nov;64(5):1059-68
references.pmid: 14573754
references.citation: PLoS One. 2012;7(1):e29420
references.pmid: 22242170
references.citation: J Pharmacol Exp Ther. 1992 Jul;262(1):119-26
references.pmid: 1625190
references.citation: J Biol Chem. 2012 Oct 5;287(41):33996-4008
references.pmid: 22893699
references.citation: Am J Respir Cell Mol Biol. 2006 Dec;35(6):621-7
references.pmid: 16902194
references.citation: J Biol Chem. 2008 Feb 29;283(9):5669-76
references.pmid: 18086673
references.citation: Am J Respir Cell Mol Biol. 2002 Apr;26(4):465-74
references.pmid: 11919083
references.citation: Biochemistry. 2005 Nov 8;44(44):14595-605
references.pmid: 16262259
references.citation: PLoS One. 2013 Jun 26;8(6):e65580
references.pmid: 23840342
references.citation: Am J Physiol Lung Cell Mol Physiol. 2008 Jan;294(1):L69-78
references.pmid: 17993590
references.citation: J Allergy Clin Immunol. 2007 Jan;119(1):235-44
references.pmid: 17208607
references.citation: Am J Respir Crit Care Med. 2005 May 15;171(10):1096-102
references.pmid: 15695490
references.citation: Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):21181-6
references.pmid: 21078968
references.citation: Am J Respir Cell Mol Biol. 1999 Nov;21(5):597-606
references.pmid: 10536119
references.citation: J Pharmacol Exp Ther. 2014 Feb;348(2):303-10
references.pmid: 24307202
references.citation: J Biol Chem. 1993 May 5;268(13):9817-23
references.pmid: 8486662
references.citation: Eur J Pharmacol. 2005 May 23;516(1):85-92
references.pmid: 15913598
references.citation: J Physiol. 1996 Jul 15;494 ( Pt 2):577-86
references.pmid: 8842014
references.citation: Am J Physiol. 1999 Apr;276(4):R1214-21
references.pmid: 10198406
references.citation: Respir Res. 2010 Sep 28;11:130
references.pmid: 20875145
references.citation: FASEB J. 2014 Feb;28(2):956-65
references.pmid: 24132623
references.citation: Mol Cell. 2004 May 7;14(3):303-17
references.pmid: 15125834
references.citation: J Biol Chem. 1984 Mar 25;259(6):3578-85
references.pmid: 6323431
references.citation: Pulm Pharmacol Ther. 2014 Feb;27(1):29-37
references.pmid: 24269928
references.citation: Chest. 1994 May;105(5):1411-9
references.pmid: 8181328
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16657-62
references.pmid: 17925438
references.citation: Mol Pharmacol. 2003 Dec;64(6):1444-51
references.pmid: 14645675
references.citation: Am J Respir Crit Care Med. 2013 Jun 15;187(12):1308-14
references.pmid: 23593932
references.citation: Am J Respir Cell Mol Biol. 2013 Feb;48(2):220-9
references.pmid: 23204390
references.citation: Respir Res. 2006 May 09;7:73
references.pmid: 16684353
references.citation: J Allergy Clin Immunol. 2011 Aug;128(2):308-14
references.pmid: 21636120