The sensitivity of the gastrointestinal tract to stress has been demonstrated in clinical settings for over half a century.1) Psychological and physical stress stimuli are associated with gastrointestinal dysfunction, including abdominal pain and diarrhea. [2][3][4] One clinical study demonstrated stress-induced alteration of colonic motility in both healthy subjects and patients with irritable bowel syndrome.5) The effects of stress on the gastrointestinal motility are conflicting: an acceleration as well as a delay of the motility by stress have been reported in small intestine, [6][7][8][9] and in colon. 7,[10][11][12][13] However, the etiology of intestinal dysfunction due to stress has not been completely clarified, and the lack of an appropriate animal model has been an obstacle to studies on the mechanism. We developed an experimental system with which to evaluate the stress effect on small intestinal motility, 14) and have since improved the system. 15) Using this improved method, we observed that small intestinal motility was inhibited by restraint stress. 15) Since it is well known that the sympathetic nervous system is strongly stimulated by acute stress, 16,17) we examined the influence of the adrenoceptor antagonists, prazosin (a 1 -antagonist), yohimbine (a 2 -antagonist), propranolol (b 1 /b 2 -antagonist), atenolol (b 1 -antagonist), ICI-118551 (b 2 -antagonist) and SR59230A (b 3 -antagonist) in order to clarify the type of adrenoceptors involved in the inhibition of small intestinal motility by restraint stress. MATERIALS AND METHODS AnimalsMale Wistar rats (6-weeks old, 150-200 g) were purchased from Japan Shizuoka Laboratory Animal Center (Hamamatsu, Japan), and were used in all the experiments according to the Guideline for Animal Experimentation of Tohoku Pharmaceutical University. The animals were housed in a wire-mesh cage [26 (W)ϫ38 (D)ϫ19 (H) cm] placed in a chamber with a constant temperature (23Ϯ1°C), humidity (55Ϯ5%) and a 12 h light-dark cycle (light 8:30 a.m. to 8:30 p.m.). The animals were given free access to tap water and rat chow.Reagents Sodium chromate ( 51 Cr) was purchased from Amersham Pharmacia Biotech (Piscataway, NJ, U.S.A.), heparin sodium from Novo Nordisk (Bagsvaerd, Denmark), pentobarbital sodium (Nembutal ® , 50 mg/ml) from Dainippon Pharmaceutical (Osaka, Japan), yohimbine HCl and DL-propranolol HCl from Nacalai Tesque (Kyoto, Japan), prazosin HCl from Sigma Aldrich Japan (Tokyo), atenolol from Wako Pure Chemicals (Tokyo), and ICI-118,551 Nawas a kind gift of Mitsubishi-Tokyo Pharmaceuticals (Tokyo). All other chemicals were of reagent grade.Cannula Implantation Cannula implantation was performed according to the method of Tsukada et al.15) The rats were anesthetized with pentobarbital sodium (50 mg/kg, i.p.), the abdomen opened by a midline incision (approximately 2-3 cm length), and a chronic indwelling silicon cannula (0.5 mm internal diameter and 0.9 mm outer diameter, medical tube SH No. 00; Kaneka, Tokyo) was inserted into the duodenum toward the jejunum and ...

We have previously reported that restraint stress inhibits small intestinal motility in rats, and that the adrenergic b b 3 -antagonist SR59230A administration recovered the inhibition. In the present study, we compared the effects of restraint stress and norepinephrine on small intestinal motility using a a-and b b-adrenergic antagonists. SR59230A did not recover the norepinephrine-induced inhibition of small intestinal motility. The norepinephrine-induced inhibition of small intestinal motility was recovered after administration of the a a 2 -antagonist yohimbine, but not by a a 1 -, b b 1 -, and b b 2 -antagonists. Considering these results, it is reasonable to assume that the mechanisms of inhibition of small intestinal motility due to restraint stress and norepinephrine treatment are different.