Basilisco G, Phillips S F
Gastroenterology Research Unit, Mayo Clinic, Rochester, MN 55903.
Aliment Pharmacol Ther. 1994 Oct;8(5):527-33. doi: 10.1111/j.1365-2036.1994.tb00326.x.
The regulatory roles of tachykinins in intestinal motor function may be clarified by use of novel, stable and selective antagonists of neurokinin receptors. We studied the effects of the non-peptide NK-2 receptor antagonist SR48968 on canine colonic tone under resting conditions and after stimulation by the selective NK-2 receptor agonist [beta Ala8] neurokinin A-(4-10).
Experiments were performed in three conscious female dogs. Proximal colonic tone was recorded by a barostat and intraluminal pressures were recorded in the terminal ileum. 10, 15 and 20 cm orad to the ileocaecal junction. In separate experiments, and in a random sequence, dogs received an i.v. injection of the NK-2 antagonist SR48968, 10, 100, 1000 micrograms/kg, followed after 30 min by 2 micrograms/kg of the agonist [beta Ala8] neurokinin A-(4-10). Experiments were replicated twice in each dog.
The NK-2 agonist increased colonic tone, and SR48968 antagonized these effects in a dose-dependent fashion (Spearman's rank, r = 0.86; P < 0.01); antagonism was complete at the highest dose. SR48968 alone had no effect on colonic tone and ileal motility. When given during phase I or II of the interdigestive motor complex, [beta Ala8] neurokinin A-(4-10) increased ileal contractions: pre-treatment with SR48968 blocked this increase in ileal motility. When given during phase III, [beta Ala8] neurokinin A-(4-10) interrupted the motility front; this effect was not antagonized by SR48968.
SR48968 antagonizes the increase in canine colonic tone and ileal motility induced by activation of NK-2 receptors. However, SR48968 by itself had no effect on the control of colonic tone and ileal motility under unstimulated conditions. SR48968 may be useful for investigating the physiological role of tachykinins on the gastrointestinal tract.
速激肽在肠道运动功能中的调节作用可通过使用新型、稳定且具选择性的神经激肽受体拮抗剂来阐明。我们研究了非肽类NK-2受体拮抗剂SR48968在静息状态下以及在选择性NK-2受体激动剂[β丙氨酸8]神经激肽A-(4-10)刺激后对犬结肠张力的影响。
实验在三只清醒的雌性犬身上进行。用压力传感器记录近端结肠张力，在回盲瓣口侧10、15和20厘米处的回肠内记录腔内压力。在单独的实验中，以随机顺序给犬静脉注射NK-2拮抗剂SR48968，剂量分别为10、100、1000微克/千克，30分钟后再注射2微克/千克的激动剂[β丙氨酸8]神经激肽A-(4-10)。每个犬重复实验两次。
NK-2激动剂增加结肠张力，SR48968以剂量依赖方式拮抗这些作用（斯皮尔曼等级相关系数，r = 0.86；P < 0.01）；在最高剂量时拮抗作用完全。单独使用SR48968对结肠张力和回肠运动无影响。在消化间期运动复合波的I期或II期给予[β丙氨酸8]神经激肽A-(4-10)时，可增加回肠收缩：预先用SR48968处理可阻断回肠运动的这种增加。在III期给予时，[β丙氨酸8]神经激肽A-(4-10)中断运动前沿；此作用未被SR48968拮抗。
SR48968拮抗NK-2受体激活诱导的犬结肠张力增加和回肠运动。然而，在未受刺激的条件下，SR48968本身对结肠张力和回肠运动的控制无影响。SR48968可能有助于研究速激肽在胃肠道中的生理作用。
