Nagakura Y, Kontoh A, Tokita K, Tomoi M, Shimomura K, Kadowaki M
Pharmacological Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
J Pharmacol Exp Ther. 1997 Apr;281(1):284-90.
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-HT4 receptor 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.
我们已经报道过，5-羟色胺3（5-HT3）受体拮抗剂未能改变清醒大鼠中5-HT加速的结肠转运，但5-HT3和5-HT4受体双重拮抗剂FK1052可阻止这种增强作用。在本研究中，对于植入近端结肠慢性插管的自由活动大鼠，5-HT4受体拮抗剂（SDZ205-557和SB204070）也未观察到对刺激的结肠转运的抑制作用。相反，同时给予昂丹司琼和5-HT4受体拮抗剂的联合拮抗作用对推进性运动产生了显著的抑制作用。此外，我们研究了5-HT受体拮抗剂对小鼠中5-HT诱导的液体分泌的影响。尽管这些选择性5-HT受体拮抗剂（作为5-HT3受体拮抗剂的YM060和昂丹司琼，作为5-HT4受体拮抗剂的SB204070）单独使用时均未对5-HT诱导的腹泻产生很大抑制作用，但5-HT3受体拮抗剂和5-HT4受体拮抗剂的组合可显著减轻腹泻。这些数据表明，5-HT加速的结肠运动和5-HT诱发的液体分泌是由5-HT3和5-HT4受体介导的，并且这些受体激活的途径可能相互协作。
