The suppressant effect of GEA3162 on spontaneous serotonin release from human colonic mucosa in vitro.
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(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.
Kojima
Shu-Ichi
S
Department of Pharmacology, Dokkyo Medical University School of Medicine, Mibu, Tochigi 321-0293, Japan. s-kojima@dokkyomed.ac.jp
Uchida
Kohsuke
K
Sasaki
Kinro
K
Sunagawa
Masakatu
M
Ohno
Yasuo
Y
Kamikawa
Yuichiro
Y
D002121:Calcium Channel Blockers / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005768:Gastrointestinal Hormones / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D045265:Natriuretic Peptides / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010069:Oxadiazoles / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D011810:Quinoxalines; D014230:Triazoles; C072685:guanylin; D030421:Peroxynitrous Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C082874:GEA 3162; D009529:Nicardipine; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D019331:NG-Nitroarginine Methyl Ester