M El-Salhy1, O Sandström. 1. Section for Gastroenterology and Hepatology, Department of Medicine, University Hospital, Umeå, Sweden. magdy.el-salhy@med.umu.se
Abstract
BACKGROUND: Motility disorders in the gastrointestinal tract increase with ageing, and colorectal carcinoma is a tumor of the middle-aged and elderly. Gastrointestinal secretion, absorption, motility, cell proliferation, local immune defense and blood flow are all regulated by the neuroendocrine peptides. It is conceivable that gastrointestinal disorders at an advanced age may be accompanied by changes in this regulatory system. OBJECTIVE: To ascertain possible age-related changes in neuroendocrine peptides in a rodent animal model. METHODS: The concentrations of various neuroendocrine peptides were determined by radioimmunoassays in tissue extracts from the antrum, duodenum and colon of mice in four different age groups: 1, 3, 12 and 24 months. The neuroendocrine peptides investigated were: secretin, gastric inhibitory polypeptide (GIP), gastrin, motilin, peptide YY (PYY), somatostatin, vasoactive intestinal polypeptide (VIP), substance P, neuropeptide Y (NPY), galanin and neurotensin. RESULTS: Antrum: Concentrations of somatostatin, VIP and substance P decreased significantly in 1-month-old mice (but that of neurotensin increased) compared with 3-month-old mice. In 12-month-old and 24-month-old mice, concentrations of gastrin, somatostatin, VIP, substance P, NPY, galanin and neurotensin all decreased vis-à-vis 3-month-old mice. Duodenum: Whereas the levels of secretin, GIP and neurotensin increased, those of gastrin, motilin, somatostatin, VIP, substance P, NPY and galanin decreased in 1-month-old mice vis-à-vis 3-month-old mice. In both 12-month-old and 24-month-old mice, the concentrations of secretin and GIP increased, compared with those of 3-month-old mice. The levels of gastrin, motilin, somatostatin, VIP, NPY and galanin decreased in both 12-month-old and 24-month-old mice vis-à-vis 3-month-old mice. Substance P and neurotensin concentrations decreased in 12-month-old mice, but not in 24-month-old mice. Colon: In 1-month-old mice the levels of PYY, somatostatin, VIP, substance P and galanin decreased vis-à-vis 3-month-old mice. In 12-month-old mice, the concentrations of PYY, somatostatin, VIP, NPY, galanin and neurotensin decreased compared with those in 3-month-old mice. In 24-month-old mice, the VIP level decreased, whereas the substance P level increased. CONCLUSION: The changes in neuroendocrine peptides observed in the gastrointestinal tract of this murine animal model could be of some relevance for the increased gastrointestinal dysfunction in the elderly human. They may also be involved in the development of colorectal cancer.
BACKGROUND:Motility disorders in the gastrointestinal tract increase with ageing, and colorectal carcinoma is a tumor of the middle-aged and elderly. Gastrointestinal secretion, absorption, motility, cell proliferation, local immune defense and blood flow are all regulated by the neuroendocrine peptides. It is conceivable that gastrointestinal disorders at an advanced age may be accompanied by changes in this regulatory system. OBJECTIVE: To ascertain possible age-related changes in neuroendocrine peptides in a rodent animal model. METHODS: The concentrations of various neuroendocrine peptides were determined by radioimmunoassays in tissue extracts from the antrum, duodenum and colon of mice in four different age groups: 1, 3, 12 and 24 months. The neuroendocrine peptides investigated were: secretin, gastric inhibitory polypeptide (GIP), gastrin, motilin, peptide YY (PYY), somatostatin, vasoactive intestinal polypeptide (VIP), substance P, neuropeptide Y (NPY), galanin and neurotensin. RESULTS: Antrum: Concentrations of somatostatin, VIP and substance P decreased significantly in 1-month-old mice (but that of neurotensin increased) compared with 3-month-old mice. In 12-month-old and 24-month-old mice, concentrations of gastrin, somatostatin, VIP, substance P, NPY, galanin and neurotensin all decreased vis-à-vis 3-month-old mice. Duodenum: Whereas the levels of secretin, GIP and neurotensin increased, those of gastrin, motilin, somatostatin, VIP, substance P, NPY and galanin decreased in 1-month-old mice vis-à-vis 3-month-old mice. In both 12-month-old and 24-month-old mice, the concentrations of secretin and GIP increased, compared with those of 3-month-old mice. The levels of gastrin, motilin, somatostatin, VIP, NPY and galanin decreased in both 12-month-old and 24-month-old mice vis-à-vis 3-month-old mice. Substance P and neurotensin concentrations decreased in 12-month-old mice, but not in 24-month-old mice. Colon: In 1-month-old mice the levels of PYY, somatostatin, VIP, substance P and galanin decreased vis-à-vis 3-month-old mice. In 12-month-old mice, the concentrations of PYY, somatostatin, VIP, NPY, galanin and neurotensin decreased compared with those in 3-month-old mice. In 24-month-old mice, the VIP level decreased, whereas the substance P level increased. CONCLUSION: The changes in neuroendocrine peptides observed in the gastrointestinal tract of this murine animal model could be of some relevance for the increased gastrointestinal dysfunction in the elderly human. They may also be involved in the development of colorectal cancer.
Authors: T Takeuchi; T Negoro; M Yamaji; Y Yamazaki; A Fujita; H Nishio; T Takewaki; K Takatsuji; F Hata Journal: Br J Pharmacol Date: 2000-11 Impact factor: 8.739