RT Journal Article
SR Electronic
T1 Combined Blockade of 5-HT<sub>3</sub>- and 5-HT<sub>4</sub>-Serotonin Receptors Inhibits Colonic Functions in Conscious Rats and Mice
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 284
OP 290
VO 281
IS 1
A1 Yasunori Nagakura
A1 Akiko Kontoh
A1 Kenichi Tokita
A1 Masaaki Tomoi
A1 Kyoichi Shimomura
A1 Makoto Kadowaki
YR 1997
UL http://jpet.aspetjournals.org/content/281/1/284.abstract
AB We have already reported that 5-hydroxytryptamine3(5-HT3) receptor antagonists failed to modify 5-HT-accelerated colonic transit in conscious rats, but the 5-HT3 and 5-HT4 receptor dual antagonist FK1052 prevented the enhancement. In this study, the inhibitory effect on the stimulated colonic transit was not also observed with 5-HT4receptor antagonists (SDZ205-557 and SB204070) in freely moving rats with chronic cannulas implanted into the proximal colon. In contrast, combined antagonism by simultaneous administration of ondansetron and the 5-HT4 receptor antagonist exerted a drastic inhibitory effect on the propulsive motility. Furthermore, we examined the effect of 5-HT receptor antagonists on 5-HT-induced fluid secretion in mice. Although none of these selective 5-HT receptor antagonists (YM060 and ondansetron as 5-HT3 receptor antagonist, SB204070 as 5-HT4 receptor antagonist) by itself produced a great inhibition of the 5-HT-induced diarrhea, the combination of a 5-HT3 receptor antagonist and a 5-HT4 receptor antagonist markedly reduced the diarrhea. These data suggest that 5-HT-accelerated colonic motility and 5-HT-evoked fluid secretion are mediated by both 5-HT3 and 5-HT4 receptors and that the pathways activated by these receptors may collaborate. The American Society for Pharmacology and Experimental Therapeutics