TY - JOUR 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 SP - 284 LP - 290 VL - 281 IS - 1 AU - Yasunori Nagakura AU - Akiko Kontoh AU - Kenichi Tokita AU - Masaaki Tomoi AU - Kyoichi Shimomura AU - Makoto Kadowaki Y1 - 1997/04/01 UR - http://jpet.aspetjournals.org/content/281/1/284.abstract N2 - 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 ER -