title: MAPKs represent novel therapeutic targets for gastrointestinal motility disorders.
abstract: The number of patients suffering from symptoms associated with gastrointestinal (GI) motility disorders is on the rise. GI motility disorders are accompanied by alteration of gastrointestinal smooth muscle functions. Currently available drugs, which can directly affect gastrointestinal smooth muscle and restore altered smooth muscle contractility to normal, are not satisfactory for treating patients with GI motility disorders. We have recently shown that ERK1/2 and p38MAPK signaling pathways play an important role in the contractile response not only of normal intestinal smooth muscle but also of inflamed intestinal smooth muscle. Here we discuss the possibility that ERK1/2 and p38MAPK signaling pathways represent ideal targets for generation of novel therapeutics for patients with GI motility disorders.
authors: Eikichi Ihara, Hirotada Akiho, Kazuhiko Nakamura, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Eikichi
authors: E
authors: Ihara
authors: Hirotada
authors: H
authors: Akiho
authors: Kazuhiko
authors: K
authors: Nakamura
authors: Sara R
authors: SR
authors: Turner
authors: Justin A
authors: JA
authors: Macdonald
references: Physiol Rev. 2003 Oct;83(4):1325-58
references: 14506307
references: J Clin Oncol. 2008 May 1;26(13):2139-46
references: 18390968
references: Trends Pharmacol Sci. 2007 Jun;28(6):286-95
references: 17482683
references: J Pharmacol Sci. 2007 Apr;103(4):427-33
references: 17409631
references: J Biochem. 1995 Dec;118(6):1104-7
references: 8720121
references: Am J Physiol Gastrointest Liver Physiol. 2009 Feb;296(2):G211-8
references: 19056759
references: Biochemistry. 2003 Mar 11;42(9):2513-23
references: 12614145
references: Stroke. 2002 Mar;33(3):775-81
references: 11872903
references: Gut. 2002 Jul;51 Suppl 1:i41-4
references: 12077063
references: J Biol Chem. 2004 Sep 3;279(36):37211-4
references: 15136561
references: Curr Opin Rheumatol. 2008 Sep;20(5):581-6
references: 18698181
references: J Biol Chem. 1988 Oct 5;263(28):14456-62
references: 3170551
references: Am J Physiol Gastrointest Liver Physiol. 2002 Aug;283(2):G390-9
references: 12121887
references: Neurogastroenterol Motil. 2010 May;22(5):e162-70
references: 20122129
references: Dig Liver Dis. 2003 Jul;35 Suppl 3:S30-4
references: 12974507
references: Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2419-24
references: 11226254
references: Clin Exp Immunol. 2006 Mar;143(3):389-97
references: 16487236
references: Biochem J. 2002 Jul 1;365(Pt 1):79-87
references: 11931630
references: Endocr Rev. 2001 Apr;22(2):153-83
references: 11294822
references: J Smooth Muscle Res. 2007 Apr;43(2):43-54
references: 17598957
references: Science. 1996 Jul 12;273(5272):245-8
references: 8662509
references: Am J Physiol Gastrointest Liver Physiol. 2005 Apr;288(4):G609-15
references: 15528258
references: Mol Pharmacol. 2009 May;75(5):1031-41
references: 19190174
references: Genes Dev. 2003 Aug 15;17(16):1969-78
references: 12893778
references: Annu Rev Physiol. 2006;68:345-74
references: 16460276
references: Am J Physiol Gastrointest Liver Physiol. 2002 Feb;282(2):G226-32
references: 11804843
references: J Pharmacol Sci. 2004 Jun;95(2):267-72
references: 15215652
references: Am J Physiol. 1989 Apr;256(4 Pt 1):G759-66
references: 2495733
references: Biochem Cell Biol. 2007 Feb;85(1):111-20
references: 17464351
references: Korean J Physiol Pharmacol. 2008 Aug;12(4):137-42
references: 19967047
references: Growth Factors. 2006 Mar;24(1):21-44
references: 16393692
references: Arch Physiol Biochem. 2003 Feb;111(1):36-44
references: 12715273
references: Biochem J. 2005 Dec 15;392(Pt 3):641-8
references: 16201970
references: Am J Physiol Gastrointest Liver Physiol. 2006 Oct;291(4):G630-9
references: 16627824
references: Gastroenterology. 2005 Aug;129(2):550-64
references: 16083712
references: Gastroenterology. 2005 Jul;129(1):131-41
references: 16012943
references: Eur J Pharmacol. 2005 May 9;514(2-3):209-15
references: 15910808
references: J Biol Chem. 2001 Aug 3;276(31):29567-74
references: 11384979
references: Arch Surg. 2002 Apr;137(4):439-45; discussion 445-6
references: 11926949
references: Biochem J. 2002 Oct 15;367(Pt 2):517-24
references: 12144526
references: Am J Physiol Gastrointest Liver Physiol. 2007 Oct;293(4):G699-710
references: 17656444
references: Ann Rheum Dis. 2006 Nov;65 Suppl 3:iii83-8
references: 17038480
references: Clin Cancer Res. 2008 Jan 15;14(2):342-6
references: 18223206
references: J Biol Chem. 2001 May 11;276(19):16365-73
references: 11278951
references: Biochem J. 2005 Aug 1;389(Pt 3):763-74
references: 15823093
references: FEBS Lett. 2000 Jun 23;475(3):197-200
references: 10869555
references: Aliment Pharmacol Ther. 2004 Jul;20 Suppl 2:1-9
references: 15335408
references: J Hematol Oncol. 2010 Feb 11;3:8
references: 20149254
references: N Engl J Med. 1993 Oct 7;329(15):1073-8
references: 8371728
references: J Gastroenterol Hepatol. 2007 Dec;22(12):2208-11
references: 18031382
references: Trends Cell Biol. 1997 Sep;7(9):353-61
references: 17708980
references: Nature. 1994 Nov 17;372(6503):231-6
references: 7969467
references: Cell. 1994 Sep 23;78(6):1027-37
references: 7923353
references: Am J Physiol. 1997 Jun;272(6 Pt 1):G1571-80
references: 9227495
references: Am J Gastroenterol. 2003 Nov;98(11):2363-71
references: 14638335
references: J Biol Chem. 1991 Jul 5;266(19):12115-8
references: 2061300
references: Gastroenterology. 1996 Dec;111(6):1683-99
references: 8942751
references: Circulation. 2007 Sep 18;116(12):1413-23
references: 17875982
references: Gastroenterology. 1993 Jun;104(6):1692-9
references: 8500728
references: Biochim Biophys Acta. 2007 Aug;1773(8):1150-60
references: 17229475
references: J Biol Chem. 2002 Jun 28;277(26):23441-6
references: 11976330