Ventromedial hypothalamic lesions increase gastrointestinal DNA synthesis through vagus nerve in rats

WS2-J-3-01 VENTROMEDIAL HYPOTHALAMIC LESIONS INCREASE GASTROINTESTINAL DNA SYNTHESIS THROUGH VAGUS NERVE IN RATS T. Kiba 1, K. Tanaka 1, S. Inoue 1'2 1) Dept. of Internal Medicine III, School of Medicine, Yokohama City Univ., Yokohama, Japan 2) The National Institute of Health and Nutrition, Tokyo, Japan. It was recently reported that ventromedial hypothalamic lesions produce an increase in gastrointestinal DNA content in rats. In the present study, the mechanisms of this alteration was examined. The DNA content, synthesis after ventromedial hypothalamic lesioning in rat gastrointestinal tracts were determined. Moreover, we examined whether the mitotic response is due to proliferation of cell population; mucosal, muscular or serosal layer. A monoclonal antibody to proliferating cell nuclear antigen (PCNA) has been previously shown to be capable of identifying proliferating cells. Alcohol-fixed gastrointestinal epithelium biopsies taken before and after VMH lesioning were immunostained with the PC-10, anti-PCNA monoclonal antibody and the labeling index was determined. Total content of DNA in stomach and small intestine began to increase at 3 days and continued to increase for 7 days, whereas DNA content in the large intestine began to increase at 3 days and maintained the same level until 7 days after ventromedial hypothalamic lesioning. DNA synthesis of these organs increased and reached maximum at 3 days and then decreased to the initial level 7 days following the lesions. Furthermore, at 1 days, sections from these organs with PCNA molecular antibody showed numerous positive cell nuclei in these organs. Labeling indices of these organs increased significantly and reached maximum at 3 days. The increase was confined to proliferation of cells in the mucosa and did not involve the residue fraction, i.e., muscularis and serosa. This increase in DNA content and synthesis in these organs was largely inhibited by bilateral subdiaphragmatic vagotomy or the administration of atropine, a cholinergic blocker, but not by the administration of anti-insulin antibody. Ventromedial hypothalamic lesions induce cell proliferation in the rat gastrointestinal tract by the firing of vagus nerve activity mainly through the cholinergic receptor mechanisms.

WS2-J-3-02 STIMULATORY SIGNALS FROM CENTRAL NERVOUS SYSTEM FOR ORNITHINE DECARBOXYLASE ACTIVITY IN RAT INTESTINAL MUCOSA K. Fujimoto, H. Morita, Y. Gotoh, S. Tsunada, T. Koyaya Div. of Gastroenterol., Dept. of Intern. Med., Saga Med. School, Saga 849, Japan It is well known that feeding plays an important role in regulating ornithine decarboxylese (ODC) activity in small intestine and that ODC activity is increased by feeding mediated through luminal nutrients. The aim of this study is to determine whether ODC activity in rat small intestine is controlled by signals from the central nervous system other than luminal nutrients. Method. Subdiaphragmatic vagotomy was accomplished under halothane anesthesia one week before experiments. In sham control rats, the vagai fibers were isolated but not cut. ODC activity in intestinal mucosa of ad libitum fed rats or 24 h fasted rats was measured at 4 time points (05:00, 11:00, 17:00, 23:00 h; light period: 08:00 to 20:00 h). In additional rats of 24 h fasted rats, ODC activity in small intestinal mucosa and liver was measured after intrathird ventricular infusion of 24 pmol 2-deoxy-glucose or 2,5-anhydro-D-mannitol at 11:00 h. Results. Table. ODC activity (C02 pmol/mg protein/h) in duodena/and jejunal mucosa of ad /ibitum fed rats. 11:00 .

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DUODENUM Vagotomy Sham JEJUNUM Vagotomy Sham

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17:00 .

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23:00 ~_ .

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05:00 .

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8.3=1.9 6.0=1.4

4.9=1.0# 37.6±3.1"

31.2±2.7* 37.2±4.7*

25.0±2.3* 24.1±1.9*

18.6=3.2 17.5---2.7

9.4±2.0 9.8±1.7

67.7±2.2* 76.0±1.8*

67.9=-5.2* 68.1+_3.9"

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*=P
174