Modification of 5-Hydroxytryptophan-Evoked 5-Hydroxytryptamine Formation of Guinea Pig Colonic Mucosa by Reactive Oxygen Species

The Japanese Journal of Pharmacology

Asako Shibukawa²  Yuichiro Kamikawa²  Masashi Ikeda¹  Shu-ichi Kojima² 

[1] Institute of Medical Science, Dokkyo University School of Medicine;Department of Pharmacology, Dokkyo University School of Medicine

关键词: 5-Hydroxytryptamine;    Colon (guinea pig);    Enterochromaffin cell;    5-Hydroxytryptophan;    Reactive oxygen species;   

DOI  :  10.1254/jjp.88.114

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(24)Cited-By(5)We studied whether reactive oxygen species (ROS) generated by normal colonic mucosa affect 5-hydroxytryptophan (5-HTP)-evoked 5-HT formation (measured as the sum of 5-HT plus 5-hydroxyindole acetic acid (5-HIAA) accumulation) of guinea pig’s isolated colonic mucosa. Catalase (3000 – 6000 U/ml), a hydrogen peroxide (H2O2) scavenger or diphenylene iodonium (DPI, 10 – 100 μM), an NADPH oxidase inhibitor, concentration-dependently caused an increase of the sum of 5-HT plus 5-HIAA accumulation in the presence of 5-HTP (10 μM), but these drugs did not significantly affect the 5-HT-metabolite in the colonic mucosa measured as the ratio of 5-HIAA/5-HT. Exogenously applied H2O2 (10 – 100 μM) concentration-dependently inhibited the sum of 5-HT plus 5-HIAA accumulation. In contrast, neither superoxide dismutase (SOD, 100 – 300 U/ml), superoxide anion scavenger, nor dimetyl sulfoxide (1 – 5%, DMSO), a hydroxyl radical scavenger affected the sum of 5-HT plus 5-HIAA accumulation. Moreover, mucosa ROS generation was estimated using the chemiluminescence technique. SOD (100 – 300 U/ml), catalase (3000 – 6000 U/ml) or DPI (10 – 100 μM), concentration-dependently reduced luminol-enhanced chemiluminescence signal from the colonic mucosa, while allopurinol (10 – 100 μM), a xanthine oxidase inhibitor, did not affect the chemiluminescence signal. These results suggest that ROS is formed through an NADPH oxidase system in the guinea pig colonic mucosa, where it exerts a modulatory effect on mucosal 5-HT formation upon addition of 5-HTP. Thus, ROS formation from normal colonic mucosa could be considered to contribute to the control of 5-HT production in mucosa enterochromaffin cells.

【 授权许可】

Unknown