Ondansetron (10 mgkg, p.0.) and granisetron (1 mgkg, p.0.) also inhibited the stress-accelerated colonic transit, but azasetron was more effective than these two drugs. Atropine methylbromide (0.1 mg/kg, s .~) and tetrodotoxin (0.01 mg/kg, s.c.) inhibited the accelerated colonic transit under stress conditions, but methysergide (10 mgkg, s.c.), SDZ205-557 (10 mg/kg, s.c.), domperidone (30 mgkg, P.o.), trimebutine (300 mgkg, P.o.), and metoclopramide (30 mgkg, p.0.) did not. Azasetron (10 pg) administered intracerebroventricularly did not inhibit the stressinduced acceleration. These results suggest that endogenous 5-HT which is released through stress accelerates the colonic transit via the 5-HT3 receptors and finally a cholinergic mechanism. It is considered that azasetron inhibits colonic transit partic- ularly under stress conditions through the blockade of the peripheral 5-HT3 receptors. Azasetron may improve bowel function in strewrelated colonic dysfunction like irritable bowel syndrome.

-Monkey cerebral artery strips partially contracted with prostaglandin F2a responded to histamine with biphasic patterns of relaxation. The delayed and sustained relaxation was suppressed by cimetidine, whereas the phasic response was abolished by treatment with chlorpheniramine and NG nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor. The inhibition by L-NA was reversed by L-arginine. D-NA was without effect. Endothelium denudation abolished the phasic relaxation. We hypothesized that endothelium-dependent, phasic relaxations caused by histamine are mediated by NO that is released by Hi-receptor stimulation, whereas the sustained relaxation is associated with the activation of H2-receptors in the smooth muscle of monkey cerebral arteries.Keywords: Histamine, Nitric oxide, Endothelium, Hi-receptor subtype, Cerebral artery (monkey)The complexity of vascular responses to histamine is based on its actions on histaminergic receptor subtypes, H1 and H2, in the endothelium and smooth muscle and on the release of chemical mediators, such as endothelium-derived relaxing factor (EDRF) and pros taglandins (PGs), from endothelial and subendothelial tissues (1 6). Histamine-induced relaxations mediated by EDRF have been reported in human, monkey and rabbit cerebral arteries (7, 8); human and monkey coronary arteries (9, 10); guinea pig pulmonary arteries (11); human umbilical vessels (12); monkey pulmonary veins (13); and rat aortas (14). The participation of EDRF is postulated from evidence that the relaxation is dependent on the endothelium and is suppressed by treatment with oxyhemoglobin, methylene blue or anti oxidants. EDRF has been proposed to be nitric oxide (NO) or an unstable S-nitroso compound that releases the NO radical (15, 16). However, endothelium-depend ent relaxations are not always associated with NO or its analog (17, 18).We have reported that endothelium-dependent re laxations caused by histamine in monkey cerebral arter ies are significantly inhibited by methylene blue and chlorpheniramine, suggesting the involvement of the endothelial H1-receptor subtype in the release of EDRF (7). Despite this conclusion, whether NO was actually involved in the response could not be determined. Methylene blue has many actions other than the inhibi tion of soluble guanylate cyclase (19,20), whereas NO synthase inhibitors, including NG-monomethyl-L-argi nine, NG-nitro-L-arginine (L-NA), L-NA methylester, etc. (21), are selective in depressing the synthesis of NO. Thus, the role of NO can be evaluated more speci fically by the use of these inhibitors. In addition, the effectiveness of NO synthase inhibitors on the endo thelium-dependent relaxation has not been evaluated in cerebral arteries.Therefore, the present study was undertaken to eluci date the involvement of endothelium-derived NO in the histamine-induced relaxation of isolated monkey cere bral arteries, with special reference to the histaminergic receptor subtypes. MATERIALS AND METHODS PreparationJapanese monkeys (Macaca fuscata) of eith...

To clarify the effect of glucocorticoid on glucose transporters (GLUT) in adipocytes and muscle, we examined the changes of GLUT4 in rat heart muscle, skeletal muscle and adipocytes during long-term administration of dexamethasone and the translocation of GLUT4. The levels of GLUT4 in the plasma membrane and the low-density microsome fraction were measured by Western blotting using anti-GLUT4 peptide antibody. The levels of GLUT4 in the heart and skeletal muscles of rat were unchanged by treatment of dexamethasone. In the adipocytes the level of GLUT4 in plasma membrane was changed, but it was decreased in the low-density microsome fraction. Although adipocytes are less involved in blood sugar regulation than skeletal muscle, this finding suggests that glucose metabolism in Cushing's syndrome is affected partly by a decrease of GLUT4 in the adipocytes.

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