Ketanserin and granisetron reduce cholera toxin-induced hypersecretion in pig jejunum.
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.
Dept. of Anatomy and Physiology, Royal Veterinary and Agricultural University, Frederiksberg, Denmark.
M B
MB
Hansen
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Skadhauge
D000818:Animals; D000831:Animals, Newborn; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology / Q000627:therapeutic use; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002772:Cholera Toxin / Q000037:antagonists & inhibitors*; D003967:Diarrhea / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D017829:Granisetron / Q000494:pharmacology* / Q000627:therapeutic use; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007419:Intestinal Secretions / Q000187:drug effects* / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D007650:Ketanserin / Q000494:pharmacology* / Q000627:therapeutic use; D008784:Methysergide / Q000494:pharmacology / Q000627:therapeutic use; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D013552:Swine; D000077526:Tropisetron
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002772:Cholera Toxin; D017829:Granisetron; D007211:Indoles; D007650:Ketanserin; D008784:Methysergide; D012702:Serotonin Antagonists; D000077526:Tropisetron; C053006:renzapride