Effects of evodiamine on gastrointestinal motility in male rats.
The effects of evodiamine on gastric emptying, gastrointestinal transit, and plasma levels of cholecystokinin (CCK) were studied in male rats. Evodiamine, isolated from the dry unripened fruit of Evodia rutaecarpa Bentham (a Chinese medicine named Wu-chu-yu), has been recommended for abdominal pain, acid regurgitation, nausea, diarrhea, and dysmenorrhea. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na(2)51CrO(4). Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Blood samples were collected for CCK radioimmunoassay (RIA). After administration of evodiamine (0.67-6.00 mg/kg), both gastric emptying and gastrointestinal transit were inhibited, whereas the plasma concentration of CCK was increased in a dose-dependent manner. The selective CCK(1) receptor antagonists, devazepide and lorglumide, effectively attenuated the evodiamine-induced inhibition of gastric emptying and gastrointestinal transit. L-365,260 (3R-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-yl)-N'-(3-methylphenyl)-urea), a selective CCK(2) receptor antagonist, did not alter the evodiamine-induced inhibition of gastric emptying and gastrointestinal transit. These results suggest that evodiamine inhibits both gastric emptying and gastrointestinal transit in male rats via a mechanism involving CCK release and CCK(1) receptor activation.
Wu
Chiu-Lung
CL
Department of Physiology, School of Medicine, National Yang-Ming University, Shih-Pai, Taipei 11221, Taiwan, ROC.
Hung
Chen-Road
CR
Chang
Full-Young
FY
Lin
Lie-Chwen
LC
Pau
K-Y Francis
KY
Wang
Paulus S
PS
D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology; D002766:Cholecystokinin / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D020109:Devazepide / Q000008:administration & dosage / Q000494:pharmacology; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology; D007274:Injections, Intraperitoneal; D008297:Male; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000494:pharmacology; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D010936:Plant Extracts; D011799:Quinazolines; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002766:Cholecystokinin; C049639:evodiamine; D020109:Devazepide