Effects of TAK-637, a novel neurokinin-1 receptor antagonist, on colonic function in vivo.
Effects of TAK-637, a novel neurokinin-1 receptor antagonist, on colonic function in vivo.
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TAK-637（一种新型神经激肽-1 受体拮抗剂）对体内结肠功能的影响。
DOI：
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发表时间：
2001
影响因子：
3.5
通讯作者：
N. Inatomi
中科院分区：
文献类型：
--
作者：
S. Okano;H. Nagaya;Y. Ikeura;H. Natsugari;N. Inatomi
P物质（Substance P， SP）是一种重要的神经递质，介导多种肠道功能；然而，其确切的病理生理作用尚不清楚。在这项研究中，我们研究了SP对结肠功能的影响，以及TAK-637 [(aR,9R)-7-[3,5-双（三氟甲基）苄基]-8,9,10,11-四氢-9-甲基-5-（4-甲基苯基）- 7h -[1,4]重氮氧基[2,1-g][1,7]萘啶-6,13-二酮]一种新的神经激肽-1 （NK1）受体拮抗剂对蒙古沙鼠对SP或应激的结肠反应的影响。SP和选择性NK1激动剂[pGlu6]SP6-11显著增加粪便颗粒产量。TAK-637减少了[pGlu6] sp6 -11诱导的排便，但对神经激肽A、5-羟色胺或碳水酚刺激的排便没有显著影响。口服TAK-637可减少约束应力刺激的粪便颗粒输出，ID50值为0.33 mg/kg。昂丹司琼和阿托品，而不是外周卡帕受体激动剂曲美布汀，也能减少约束应激刺激的排便。TAK-637抑制脑室内注射促肾上腺皮质激素释放因子刺激的粪球输出量的增加，但不影响应激诱导的血浆促肾上腺皮质激素水平的升高。辣椒素对感觉神经元的去神经支配不影响应激刺激的排便。这些结果表明，肠丛中的NK1受体在应激诱导的结肠功能变化中起重要作用，TAK-637可能有助于治疗肠易激综合征等功能性肠病。
Substance P (SP) is an important neurotransmitter that mediates various gut functions; however, its precise pathophysiological role remains unclear. In this study, we investigated the effect of SP on colonic function and the effect of TAK-637 [(aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10,11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g][1,7]naphthyridine-6,13-dione] a new neurokinin-1 (NK1) receptor antagonist, on colonic responses to SP or stress in Mongolian gerbils. SP and the selective NK1 agonist [pGlu6]SP6-11 significantly increased fecal pellet output. TAK-637 reduced [pGlu6]SP6-11-induced defecation, but did not significantly affect neurokinin A-, 5-hydroxytryptamine- or carbachol-stimulated defecation. Oral TAK-637 decreased restraint stress-stimulated fecal pellet output with an ID50 value of 0.33 mg/kg. Ondansetron and atropine, but not the peripheral kappa-receptor agonist trimebutine, also reduced restraint stress-stimulated defecation. TAK-637 inhibited the increase in fecal pellet output stimulated by intracerebroventricular injection of corticotropin-releasing factor, but did not affect the stress-induced increase in plasma adrenocorticotropic hormone levels. Denervation of the sensory neurons with capsaicin did not affect stress-stimulated defecation. These results suggest that NK1 receptors in the enteric plexus play an important role in stress-induced changes in colonic function, and that TAK-637 may be useful in the treatment of functional bowel diseases such as irritable bowel syndrome.
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DOI：
10.1152/ajpgi.1987.253.4.g582
发表时间：
1987-10
期刊：
The American journal of physiology
影响因子：
--
作者：
C. L. Williams;J. M. Peterson;R. Villar;T. Burks
通讯作者：
C. L. Williams;J. M. Peterson;R. Villar;T. Burks
影响因子：
29.4
作者：
W. Whitehead;O. Palsson
通讯作者：
W. Whitehead;O. Palsson
DOI：
10.1152/ajpgi.1989.256.1.g246
发表时间：
1989
期刊：
The American journal of physiology
影响因子：
--
作者：
Koelbel,CB;Mayer,EA;ReeveJr,JR;SnapeJr,WJ;Patel,A;Ho,FJ
通讯作者：
Ho,FJ
影响因子：
29.4
作者：
WILLIAMS, CL;VILLAR, RG;BURKS, TF
通讯作者：
BURKS, TF