T. Endo et al., GRANISETRON, A 5-HT3 RECEPTOR ANTAGONIST, INHIBITED CISPLATIN-INDUCED5-HYDROXYTRYPTAMINE RELEASE IN THE ISOLATED ILEUM OF FERRETS, Research communications in molecular pathology and pharmacology, 100(3), 1998, pp. 243-253
We investigated the influence of granisetron, a 5-HT3 receptor antagon
ist, on the increase in 5-hydroxytryptamine (5-HT) release induced by
cisplatin from the isolated ileum of the ferret, a species known to vo
mit in response to cisplatin. 2-Methyl-5-MT, a selective 5-HT, recepto
r agonist, increased the release of 5-HT from the ferret ileum in a co
ncentration-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 rele
ase. Since the cisplatin-induced 5-HT release was significantly inhibi
ted by tetrodotoxin, the possible involvement of an interneuron pathwa
y in the cisplatin-induced 5-HT release mechanism was suggested in the
ileal tissue. It is likely that granisetron inhibited the cisplatin-i
nduced 5-HT release from the gut EC cells by producing blockade of an
EC cell 5-HT3 receptor.