Abstract
The aim of this study was to investigate whether the central nervous system regulates mucosal cell growth and apoptosis in the rat small intestine. Ornithine decarboxylase is a key enzyme for polyamine synthesis, which plays an important role in intestinal mucosal growth. The increase in ornithine decarboxylase activity in the duodenum just before a dark period was abolished by truncal vagotomy. An infusion of 2-deoxy-D-glucose into the third cerebroventricle activated the enzyme activity in the small intestine. Epithelial homeostasis is balanced by the regulation of cell proliferation and cell death. Intestinal mucosal apoptosis decreased in rats with ventromedial hypothalamus lesions, which induced hyperphagia and obesity. In contrast, sustained anorexia induced by 1-deoxy-D-glucosamine increased intestinal apoptosis. These results indicate that the central nervous system, in addition to local factors, is related to the regulation of mucosal homeostasis in the intestinal mucosa.
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References
Johnson LR. Regulation of gastrointestinal mucosal growth. Physiol Rev 1998;68:456–502.
Moore P, Swendseid ME. Dietary regulation of the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase in rats. J Nutr 1983;113:1927–35.
Tabata K, Johnson LR. Mechanism of induction of mucosal ornithine decarboxylase by food. Am J Physiol 1986;251:G370–4.
Hirano M, Iwakiri R, Fujimoto K, Sakata H, Ohyama T, Sakai T, et al. Epidermal growth factor enhances repair of rat intestinal mucosa damaged by oral administration of methotrexate. J Gastroenterol 1995;30:169–76.
Ulshen MH, Lyn-Cook L, Raasch RH. Effects of intraluminal epidermal growth factor on mucosal proliferation in the small intestine of adult rats. Gastroenterology 1986;91:1134–40.
Maudsley DV, Leif J, Kobayashi Y. Ornithine decarboxylase in rat small intestine: stimulation with food or insulin. Am J Physiol 1976;231:1557–61.
Meleagros L, Ghatei MA, Bloom SR. Release of vasodilator, but not vasoconstrictor, neuropeptides and enteroglucagon by intestinal ischemia/reperfusion in the rat. Gut 1994;35:1701–6.
Sagor GR, Ghatei MA, Al-Mukhtar MYT, Wright NA, Bloom SR. Evidence for a humoral mechanism after small intestinal resection. Gastroenterology 1983;84:902–6.
Fujimoto K, Imamura I, Granger DN, Wada H, Sakata T, Tso P. Histamine and histidine decarboxylase are correlated with mucosal repair in rat small intestine after ischemia-reperfusion. J Clin Invest 1992;89:126–33.
Tsunada S, Fujimoto K, Gotoh Y, Sakai T, Kang M, Sakata T, et al. Role of histamine receptors in intestinal repair after ischemia-reperfusion in rats. Gastroenterology 1994;107:1297–304.
Tanaka J, Fujimoto K, Sakata T, Fujimoto T, Tsunada S, Iwakiri R, et al. Effect of vagotomy on ornithine decarboxylase activity in rat duodenal mucosa. Am J Physiol 1993;265:G1016–20.
Fujimoto K, Morita H, Matsunaga C, Ogata S, Furukawa N, Sakata Y, et al. Stimulatory signals from central nervous system for ornithine decarboxylase activity in the rat duodenal mucosa. Pathophysiology 1995;2:25–8.
Morita H, Fujimoto K, Sakata T, Kurokawa M, Yoshimatsu H, Noda T, et al. Ornithine decarboxylase activity in rat intestinal mucosa and liver is stimulated by central administration of 2-deoxy-D-glucose but not of 2,5-anhydro-D-mannitol. Brain Res 1996;719:112–6.
Matsunaga C, Fujimoto K, Iwakiri R, Koyama T, Ogata S, Gotoh Y, et al. Lingual factors enhance the increase of ornithine decarboxylase activity in rat jejunal mucosa after feeding. Metabolism 1996;45:1284–7.
Fujimoto K, Iwakiri R, Utsumi H, Kojima M, Ishibashi S, Wu B, et al. Effect of the central nervous system on mucosal growth and apoptosis in the small intestine. Digestion 2001;63 Suppl 1:108–11.
Iwakiri R, Gotoh Y, Noda T, Sugihara H, Fujimoto K, Fuseler J, et al. Programmed cell death in rat intestine: effect of feeding and fasting. Scand J Gastroenterol 2001;36:39–47.
Fujimoto K, Sakata T, Shiraishi T, Kurata K, Terada K, Etou H. Anorexia induced in rats by D-glucosamine deoxidized at C-l. Am J Physiol 1986;251:R481–91.
Shiraishi T, Simpson A. Central control of gastric acid secretion by extralateral hypothalamic nuclei. Brain Res Bull 1987;18:309–14.
Aw TY, Nicotera P, Manzo L, Orrenius S. Tributyltin stimulates apoptosis in rat thymocytes. Arch Biochem Biophys 1990;283:46–50.
Noda T, Iwakiri R, Fujimoto K, Matuo S, Aw TY. Programmed cell death induce by ischemia-reperfusion in rat intestinal mucosa. Am J Physiol 1998;274:G270–6.
Wyllie AH. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 1980; 284:555–6.
Kashiwagi Y, Fujimoto K, Iwakiri R, Yoshida T, Noda T, Aw TY, et al. Loss of diurnal variation in ornithine decarboxylase and apoptosis in small intestine of Mongolian gerbils. 2000;35:434–40.
Fujimoto M, Kanaya A, Nakabou Y, Hagihira H. Circadian rhythm in the ornithine decarboxylase activity of rat small intestine. J Biochem 1978;83:237–42.
Fujimoto K, Granger DN, Johnson LR, Price VH, Sakata T, Tso P. Circadian rhythm of ornithine decarboxylase activity in small intestine of fasted rats. Proc Soc Exp Biol Med 1992;100:409–13.
Kurokawa M, Sakata T, Yoshimatsu H, Machidori H. 2,5- Anhydro-D-mannitol: its unique central action on food intake and blood glucose in rats. Brain Res 1991;566:270–5.
Sakata T, Kurokawa M. Feeding modulation by pentose and hexose analogues. Am J Clin Nutr 1992;55:272S–7S.
Fukagawa K, Sakata T, Shiraishi T, Yoshimatsu H, Fujimoto K, Ookuma K, et al. Neuronal histamine modulates feeding behavior through H1-receptor in rat hypothalamus. Am J Physiol 1989;256: R605–11.
Goldfien A, Gangong WF. Adrenal medullary and adrenal cortical response to stimulation of diencephalon. Am J Physiol 1962;202:205–ll.
Shiraishi T, Simpson A. Lateral hypothalamus neuron responses to electroosmotic 2-deoxy-D-glucose. Brain Res Bull 1982;8:645–51.
Katafuchi T, Oomura Y, Yoshimatsu H. Single neuron activity in the rat lateral hypothalamus during 2-deoxy-d-glucose-induced and natural feeding behavior. Brain Res 1985;359:l–9.
Balagura S, Kanner M. Hypothalamic sensitivity to 2-deoxy-d- glucose and glucose: effects on feeding behavior. Physiol Behav 1971;7:251–5.
Hanson RL, Ho RS, Wisenberg JJ, Simpson R, Younathan ES, Blair JB. Inhibition of gluconeogenesis and glycogenolysis by 2,5-anhydro-d-mannitol. J Biol Chem 1984;259:218–33.
Stevens HC, Covey TR, Dills WL. Inhibition of gluconeogenesis by 2,5-anhydro-D-mannitol in isolated rat hepatocytes. Biochem Biophys Acta 1985;845:502–6.
Ono T, Sasaki K, Nishino H, Fukuda M, Shibata R. Feeding and diurnal related activity of lateral hypothalamic neurons in freely behaving rats. Brain Res 1986;373:92–102.
Shiraishi T. Effects of lateral hypothalamic stimulation on medulla oblongata and gastric vagal neural responses. Brain Res Bull 1980;5:245–50.
Oomura Y, Yoshimatsu H. Neural network of glucose monitoring system. J Auton Nerv Syst 1984;10:359–72.
Yoshimatsu H, Niijima A, Oomura Y, Katafuchi T. Lateral and ventromedial hypothalamic influences on hepatic nerve activity in the rat. Brain Res Bull 1988;21:239–44.
Kiba T, Tanaka K, Endo O, Inoue S. Ventromedial hypothalamic lesions increase gastrointestinal DNA synthesis through vagus nerve in rats. Gastroenterology 1993;104:475–84.
Kiba T, Tanaka K, Numata K, Hoshino M, Nisugi K, Inoue S. Ventromedial hypothalamic lesion-induced vagal hyperactivity stimulates rat pancreatic cell proliferation. Gastroenterology 1996;110:885–93.
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Fujimoto, K., Iwakiri, R., Wu, B. et al. Homeostasis in the small intestinal mucosa balanced between cell proliferation and apoptosis is regulated partly by the central nervous system. J Gastroenterol 37 (Suppl 14), 139–144 (2002). https://doi.org/10.1007/BF03326433
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DOI: https://doi.org/10.1007/BF03326433