Granisetron, a 5-HT3 receptor antagonist, inhibited cisplatin-induced 5-hydroxytryptamine release in the isolated ileum of ferrets

Endo, T.; Ogawa, T.; Hamaue, N.; Akita, K.; Hirafuji, M.; Minami, M.; Blower, P.R.

Research Communications in Molecular Pathology and Pharmacology 100(3): 243-253

1998


ISSN/ISBN: 1078-0297
PMID: 9730004
Document Number: 1005
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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Granisetron, a 5-HT3 receptor antagonist, inhibited cisplatin-induced 5-hydroxytryptamine release in the isolated ileum of ferrets