Tuladhar Bishwa R, Ge Lanbo, Naylor Robert J
Bradford School of Pharmacy, University of Bradford, Bradford BD7 1DP.
Br J Pharmacol. 2003 Apr;138(7):1210-4. doi: 10.1038/sj.bjp.0705184.
The study was undertaken to investigate the 5-HT receptor mediating the inhibitory effect of 5-HT on peristalsis in the guinea-pig isolated ileum. The facilitatory and inhibitory effects were measured as the decrease and increase, respectively, in the intraluminal pressure required to trigger peristalsis. In the presence of 5-HT(2/3&4) receptor antagonists ketanserin (0.1 micro M), granisetron (1 micro M) and SB-204070 (1 micro M), a cumulative addition (0.1-100 micro M) of 5-HT or 5-carboxamidotryptamine, but not 2-methyl-5-HT produced a concentration-dependent increase in the threshold required to trigger peristalsis. The 5-HT(7) receptor selective antagonist SB-269970-A (0.01-1 micro M) or methiothepin (0.01-0.1 micro M) concentration-dependently antagonised this response to 5-HT. SB-269970-A (1 micro M) and methiothepin (1 micro M) were also able to restore peristalsis in tissues in which peristalsis was inhibited by a prior addition of 30 micro M of 5-HT. The results indicate an involvement of 5-HT(7) receptors in the inhibitory effect of 5-HT on peristalsis in the guinea-pig ileum.
本研究旨在探究介导5-羟色胺(5-HT)对豚鼠离体回肠蠕动产生抑制作用的5-HT受体。促进和抑制作用分别通过触发蠕动所需的腔内压力降低和升高来衡量。在存在5-HT(2/3&4)受体拮抗剂酮色林(0.1微摩尔)、格拉司琼(1微摩尔)和SB-204070(1微摩尔)的情况下,5-HT或5-羧酰胺色胺(而非2-甲基-5-HT)的累积添加(0.1 - 100微摩尔)会使触发蠕动所需的阈值呈浓度依赖性增加。5-HT(7)受体选择性拮抗剂SB-269970-A(0.01 - 1微摩尔)或甲硫哒嗪(0.01 - 0.1微摩尔)可浓度依赖性地拮抗对5-HT的这种反应。SB-269970-A(1微摩尔)和甲硫哒嗪(1微摩尔)还能够使先前添加30微摩尔5-HT而抑制蠕动的组织恢复蠕动。结果表明5-HT(7)受体参与了5-HT对豚鼠回肠蠕动的抑制作用。