Granisetron, a 5-HT3 receptor antagonist, inhibited cisplatin-induced 5-hydroxytryptamine release in the isolated ileum of ferrets.
We investigated the influence of granisetron, a 5-HT3 receptor antagonist, on the increase in 5-hydroxytryptamine (5-HT) release induced by cisplatin from the isolated ileum of the ferret, a species known to vomit in response to cisplatin. 2-Methyl-5-HT, a selective 5-HT3 receptor agonist, increased the release of 5-HT from the ferret ileum in a concentration-dependent manner within the range of 10(-7) to 10(-6)M. The 5-HT release induced by 2-methyl-5-HT was significantly inhibited by a concomitant perfusion with granisetron (10(-6)M). Cisplatin also increased the 5-HT release from the ferret ileum within the range of 10(-8) to 10(-6)M, in a concentration-dependent manner. Granisetron (10(-6)M) also significantly inhibited the cisplatin-induced 5-HT release. Since the cisplatin-induced 5-HT release was significantly inhibited by tetrodotoxin, the possible involvement of an interneuron pathway in the cisplatin-induced 5-HT release mechanism was suggested in the ileal tissue. It is likely that granisetron inhibited the cisplatin-induced 5-HT release from the gut EC cells by producing blockade of an EC cell 5-HT3 receptor.
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Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.
Ogawa
T
T
Hamaue
N
N
Akita
K
K
Hirafuji
M
M
Minami
M
M
Blower
P R
PR
D000818:Animals; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005289:Ferrets; D017829:Granisetron / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011985:Receptors, Serotonin / Q000187:drug effects*; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D002945:Cisplatin; D017829:Granisetron; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin; D012702:Serotonin Antagonists; D013779:Tetrodotoxin; C045918:2-methyl-5-HT