부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ejphar.2006.08.047 Byline: Shu-ichi Kojima (a), Kohsuke Uchida (a), Kinro Sasaki (b), Masakatu Sunagawa (b), Yasuo Ohno (c), Yuichiro Kamikawa (a) Keywords: GEA3162; Guanylin; Human colon; l-N.sup.G-nitroarginine methyl ester; Nicardipine; Serotonin release Abstract: The effect of a lipophilic nitric oxide (NO)-releasing compound 5-amino-3-(3,4-dichlorophenyl) 1,2,3,4-oxatriazolium (GEA3162) on the spontaneous release of 5-hydroxytryptamine (5-HT) from human colonic mucosa was investigated in vitro. In the presence of tetrodotoxin, spontaneous outflow of 5-HT from the human colonic mucosa was measured by high-performance liquid chromatography with electrochemical detection. GEA3162 concentration-dependently suppressed the 5-HT outflow, but neither the NO-activated soluble guanylate cyclase inhibitor 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) nor peroxynitrite scavenger ebselen affected the suppressant effect of GEA3162. Moreover, neither the L-type calcium channel blocker nicardipine, NO synthase inhibitor l-N.sup.G-nitroarginine methyl ester nor guanylate cyclase activator guanylin affected the spontaneous 5-HT outflow. These results indicate that human colonic mucosa is capable of eliciting tetrodotoxin-resistant and nicardipine-insensitive 5-HT release, and that GEA3162 can suppress the 5-HT release via an action on colonic mucosa through mechanism independent of ODQ-sensitive cyclic GMP system or peroxynitrite generation. Author Affiliation: (a) Department of Pharmacology, Dokkyo Medical University School of Medicine, Mibu, Tochigi 321-0293, Japan (b) Surgery, Dokkyo Medical University School of Medicine, Mibu, Tochigi 321-0293, Japan (c) Division of Pharmacology, National Institute of Hygienic Science, Setagaya, Tokyo 158-8501, Japan Article History: Received 10 May 2006; Revised 22 August 2006; Accepted 23 August 2006