Ketanserin and granisetron reduce cholera toxin-induced hypersecretion in pig jejunum. 1994

M B Hansen, and E Skadhauge
Dept. of Anatomy and Physiology, Royal Veterinary and Agricultural University, Frederiksberg, Denmark.

BACKGROUND Serotonin antagonists have been proven antisecretory in cholera toxin (CT)-induced hypersecretion in the small intestine of rodents. The pig small intestine is a good model for the human small intestine with regard to physiologic and pharmacologic processes. METHODS The antisecretory effect of intraluminally administered methysergide, renzapride, ketanserin, granisetron, and tropisetron on CT-induced hypersecretion was tested in isolated pig jejunal loops in vivo. RESULTS Methysergide, ketanserin, and granisetron reduced the hypersecretory effect of CT maximally by 25%, 80%, and 50%, respectively. Tropisetron enhanced whereas renzapride did not alter the CT response. Combination of ketanserin and granisetron gave a maximal inhibitory effect of about 85%. Surprisingly, renzapride, granisetron, and tropisetron each induced hypersecretion. Taking into account the hypersecretory effect of the antagonists, they all reduced this CT-elicited hypersecretion. CONCLUSIONS Results suggest involvement of the 5-hydroxytryptamine-2 and 5-hydroxytryptamine-3 receptor subtypes as mediators in CT-induced hypersecretion in pig jejunum, and antidiarrheal therapeutic potentials of ketanserin and granisetron.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D007419 Intestinal Secretions Fluids originating from the epithelial lining of the intestines, adjoining exocrine glands and from organs such as the liver, which empty into the cavity of the intestines. Intestinal Secretion,Secretion, Intestinal,Secretions, Intestinal
D007583 Jejunum The middle portion of the SMALL INTESTINE, between DUODENUM and ILEUM. It represents about 2/5 of the remaining portion of the small intestine below duodenum. Jejunums
D007650 Ketanserin A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients. 3-(2-(4-(4-Fluorobenzoyl)piperidinol)ethyl)-2,4(1H,3H)-quinazolinedione,R-41,468,R-41468,R 41,468,R 41468,R41,468,R41468
D008784 Methysergide An ergot derivative that is a congener of LYSERGIC ACID DIETHYLAMIDE. It antagonizes the effects of serotonin in blood vessels and gastrointestinal smooth muscle, but has few of the properties of other ergot alkaloids. Methysergide is used prophylactically in migraine and other vascular headaches and to antagonize serotonin in the carcinoid syndrome. Dimethylergometrin,Methylmethylergonovine,Deseril,Desril,Désernil-Sandoz,Methysergide Dimaleate,Methysergide Maleate,Sansert,UML-491,Dimaleate, Methysergide,Désernil Sandoz,Maleate, Methysergide,UML 491,UML491
D002772 Cholera Toxin An ENTEROTOXIN from VIBRIO CHOLERAE. It consists of two major protomers, the heavy (H) or A subunit and the B protomer which consists of 5 light (L) or B subunits. The catalytic A subunit is proteolytically cleaved into fragments A1 and A2. The A1 fragment is a MONO(ADP-RIBOSE) TRANSFERASE. The B protomer binds cholera toxin to intestinal epithelial cells and facilitates the uptake of the A1 fragment. The A1 catalyzed transfer of ADP-RIBOSE to the alpha subunits of heterotrimeric G PROTEINS activates the production of CYCLIC AMP. Increased levels of cyclic AMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. Cholera Toxin A,Cholera Toxin B,Cholera Toxin Protomer A,Cholera Toxin Protomer B,Cholera Toxin Subunit A,Cholera Toxin Subunit B,Choleragen,Choleragenoid,Cholera Enterotoxin CT,Cholera Exotoxin,Cholera Toxin A Subunit,Cholera Toxin B Subunit,Procholeragenoid,Enterotoxin CT, Cholera,Exotoxin, Cholera,Toxin A, Cholera,Toxin B, Cholera,Toxin, Cholera
D003967 Diarrhea An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight. Diarrheas
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D000077526 Tropisetron An indole derivative and 5-HT3 RECEPTOR antagonist that is used for the prevention of nausea and vomiting. (3 alpha-Tropanyl)-1H-indole-3-carboxylic Acid Ester,ICS 205-930,ICS-205-930,ICS-205930,Indole-3-carboxylic Acid Tropine Ester,Navoban,Tropisetron Hydrochloride,ICS 205 930,ICS 205930,Indole 3 carboxylic Acid Tropine Ester

Related Publications

M B Hansen, and E Skadhauge
February 1995, Pharmacology & toxicology,
M B Hansen, and E Skadhauge
June 1977, Medical biology,
M B Hansen, and E Skadhauge
May 1997, Lancet (London, England),
M B Hansen, and E Skadhauge
August 1992, Japanese journal of medical science & biology,
M B Hansen, and E Skadhauge
April 1982, Acta pharmacologica et toxicologica,
M B Hansen, and E Skadhauge
August 1983, Acta pathologica, microbiologica, et immunologica Scandinavica. Section B, Microbiology,
M B Hansen, and E Skadhauge
September 1997, European journal of gastroenterology & hepatology,
M B Hansen, and E Skadhauge
September 1992, Gut,
Copied contents to your clipboard!