title: Impaired colonic motility and reduction in tachykinin signalling in the aged mouse.
abstract: Ageing is associated with an increased incidence of constipation in humans. The contribution that the ageing process makes to this condition is unclear. The aim of this study was to determine the effects of age on faecal output and colonic motility in male C57BL/6J mice and to determine the role that altered tachykinin signalling plays in this process. Total faecal output recorded over a 24h period decreased with age due to a reduction in the number of pellets produced and their water content. These changes occurred in the absence of any significant change in food and water intake. There was an increase in the amount of faecal matter stored in the isolated colon with age which caused a proportional increase in colonic length. Analysis of colonic motility using an artificial pellet demonstrated that pellets moved in a stepwise fashion through the colon. There was an age-related increase in pellet transit time due to decreases in the step distance, velocity, and frequency of stepwise movements. These changes were reversed using the neurokinin 2 (NK2) receptor agonist neurokinin A. Addition of the NK2receptor antagonist GR159897 significantly increased transit time in the young animals by decreasing step distance, velocity and frequency, but was without effect in the aged colon. In summary, the ageing C57BL/6J mouse shows an impaired motility phenotype. These effects appear, at least in part, to be due to an attenuation of tachykinin signalling via NK2 receptors.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Huxley Building, University of Brighton, Lewes Road, Brighton BN2 4GJ, UK.
authors.forename: Bhavik Anil
authors.initials: BA
authors.lastname: Patel
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Huxley Building, University of Brighton, Lewes Road, Brighton BN2 4GJ, UK.
authors.forename: Nikkita
authors.initials: N
authors.lastname: Patel
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Huxley Building, University of Brighton, Lewes Road, Brighton BN2 4GJ, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Fidalgo
authors.affiliation: Department of Life, Health and Chemical Sciences, Biomedical Research Network, Open University, Walton Hall, Milton Keynes MK7 6AA, UK.
authors.forename: Chunfang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Faculty of Health and Life Sciences, Northumbria University, Ellison Building, Newcastle upon Tyne NE1 8ST, UK.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Ranson
authors.affiliation: Department of Life, Health and Chemical Sciences, Biomedical Research Network, Open University, Walton Hall, Milton Keynes MK7 6AA, UK.
authors.forename: M Jill
authors.initials: MJ
authors.lastname: Saffrey
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Huxley Building, University of Brighton, Lewes Road, Brighton BN2 4GJ, UK. Electronic address: m.s.yeoman@brighton.ac.uk.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Yeoman
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D003106:Colon / Q000502:physiology*; D003672:Defecation / Q000502:physiology; D005243:Feces; D005769:Gastrointestinal Motility / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018041:Receptors, Neurokinin-2 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D015320:Tachykinins / Q000378:metabolism*
chemical_list: D018041:Receptors, Neurokinin-2; D015320:Tachykinins
keywords: Ageing; Faecal output; Impaired colonic motility; Neurokinin A; Tachykinin