title: Age-related changes in melatonin release in the murine distal colon.
abstract: Constipation and fecal impaction are conditions of the bowel whose prevalence increases with age. Limited information is known about how these conditions manifest; however, functional deficits are likely to be due to changes in signaling within the bowel. This study investigated the effects of age on colonic mucosal melatonin (MEL) release and the consequences this had on colonic motility. Electrochemical measurements of MEL overflow demonstrated that both basal and mechanically stimulated MEL release decreased with age. The MEL/serotonin also decreased with increasing age, and the trend was similar to that of MEL overflow, suggestive that age-related changes were primarily due to a reduction in MEL levels. Levels of N-acetylserotonin and the N-acetylserotonin/serotonin ratio were reduced with age, providing an explanation for the reduction in MEL release. Decreases in colonic motility were observed in animals between 3 and 24 months old. Exogenous application of MEL could reverse this deficit in aged colon. In summary, we propose that the age-related decline in MEL release may be due to either decreases or alterations in mechanosensory channels and/or a loss in levels/activity of the N-acetyltransferase enzyme responsible for the synthesis of N-acetylserotonin. Decreases in MEL release may explain the decreases in colonic motility observed in 24 month old animals and could offer a new potential therapeutic treatment for age-related constipation.
authors: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, United Kingdom.
authors: Lucy B
authors: LB
authors: Diss
authors: Stephen D
authors: SD
authors: Robinson
authors: Yukyee
authors: Y
authors: Wu
authors: Sara
authors: S
authors: Fidalgo
authors: Mark S
authors: MS
authors: Yeoman
authors: Bhavik Anil
authors: BA
authors: Patel
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003106:Colon / Q000378:metabolism*; D055664:Electrochemical Techniques; D004759:Enterochromaffin Cells / Q000378:metabolism / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D063206:N-Terminal Acetyltransferases / Q000502:physiology; D012701:Serotonin / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D012701:Serotonin; D063206:N-Terminal Acetyltransferases; D008550:Melatonin; C006389:N-acetylserotonin
references: Analyst. 2008 Apr;133(4):516-24
references: 18365122
references: Chem Biol. 2001 Apr;8(4):379-89
references: 11325593
references: Neuro Endocrinol Lett. 2002 Apr;23(2):121-32
references: 12011798
references: Dig Dis Sci. 2009 May;54(5):1087-93
references: 18720001
references: J Pineal Res. 2011 Nov;51(4):405-15
references: 21649718
references: Aliment Pharmacol Ther. 2004 Nov;20 Suppl 7:3-14
references: 15521849
references: Analyst. 2007 Jan;132(1):41-7
references: 17180178
references: Br J Pharmacol. 2011 Mar;162(5):1179-85
references: 21091649
references: Neurogastroenterol Motil. 2013 Jul;25(7):e495-e505
references: 23517051
references: Acta Neurobiol Exp (Wars). 1992;52(4):265-74
references: 1293965
references: Adv Exp Med Biol. 1991;294:221-30
references: 1772068
references: N Engl J Med. 2000 Oct 12;343(15):1114-6
references: 11027748
references: Mech Ageing Dev. 2004 Dec;125(12):899-906
references: 15563936
references: J Pineal Res. 1994 Mar;16(2):91-9
references: 8014829
references: Comp Biochem Physiol B Biochem Mol Biol. 1995 Oct;112(2):251-5
references: 7584855
references: Eur J Pharmacol. 1996 Oct 3;312(3):319-25
references: 8894614
references: Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):787-91
references: 8290600
references: Manag Care Interface. 2006 Dec;19(12):43-9
references: 17274481
references: Curr Gastroenterol Rep. 2010 Dec;12(6):507-12
references: 20878508
references: Aliment Pharmacol Ther. 2005 Nov 15;22(10):927-34
references: 16268966
references: Best Pract Res Clin Gastroenterol. 2011 Feb;25(1):59-71
references: 21382579
references: J Comp Physiol B. 2009 Nov;179(8):951-9
references: 19543897
references: Aliment Pharmacol Ther. 2010 May;31(9):938-49
references: 20180788
references: Clin Interv Aging. 2010 Aug 09;5:163-71
references: 20711435
references: Experientia. 1977 May 15;33(5):662-3
references: 324794
references: Neurogastroenterol Motil. 2009 Jul;21(7):746-e46
references: 19220755
references: Best Pract Res Clin Gastroenterol. 2009;23(6):875-87
references: 19942165
references: Biol Signals Recept. 2001 Nov-Dec;10(6):350-66
references: 11721091
references: Dig Dis Sci. 2002 Oct;47(10):2336-48
references: 12395907
references: J Pineal Res. 2010 Aug;49(1):23-34
references: 20374441
references: Curr Top Med Chem. 2002 Feb;2(2):181-97
references: 11899100
references: Neurogastroenterol Motil. 2010 Dec;22(12):e364-73
references: 20939846
references: Biull Eksp Biol Med. 1976;82(11):1400-1
references: 797405
references: J Pharm Biomed Anal. 1999 Feb;19(1-2):33-46
references: 10698566
references: Gastroenterol Clin North Am. 2001 Jun;30(2):497-515
references: 11432302
references: Curr Med Chem. 2002 Jun;9(12):1187-99
references: 12052171
references: Endocr Rev. 1991 May;12(2):151-80
references: 1649044
references: J Pineal Res. 1986;3(3):277-84
references: 3021949
references: Neurogastroenterol Motil. 2004 Apr;16 Suppl 1:19-23
references: 15065999