速激肽刺激的小肠肌电模式：一氧化氮抑制的致敏作用及神经激肽受体阻断的逆转作用

Tachykinin-stimulated small bowel myoelectric pattern: sensitization by NO inhibition, reversal by neurokinin receptor blockade.

作者信息

Schmidt Peter Thelin, Bozkurt Ayhan, Hellström Per M

机构信息

Gastroenterology Unit, Department of Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.

出版信息

Regul Pept. 2002 Apr 15;105(1):15-21. doi: 10.1016/s0167-0115(01)00369-x.

DOI:10.1016/s0167-0115(01)00369-x

PMID:11853867

Abstract

UNLABELLED

Tachykinins stimulate motility whereas NO inhibits motility in the gastrointestinal tract.

AIM

To investigate if inhibition of NO production sensitizes myoelectric activity to subthreshold doses of tachykinins in the small intestine of awake rats.

METHODS

Rats were supplied with a venous catheter and bipolar electrodes at 5, 15 and 25 cm distal to pylorus for electromyography of small intestine. The motor responses were evaluated using pattern recognition. Substance P and neurokinin A dose-dependently stimulated gut motility, with neurokinin A being more potent than substance P. Therefore, neurokinin A was chosen and administered under baseline conditions and 45-60 min after N(omega)-nitro-L-arginine (L-NNA) 1 mg kg(-1), with or without pretreatment with L-arginine 300 mg kg(-1). In addition, myoelectric activity effects of neurokinin A in conjunction with L-NNA were studied before and after administration of the tachykinin receptor antagonists, SR140333 (NK1), SR48968 (NK2) and SR142801 (NK3), each at 2.5 mg kg(-1).

RESULTS

Dose-finding studies verified 10 pmol kg(-1) min(-1) to be the threshold dose at which NKA caused phase II-like activity in a low percentage of experiments (12%, n=41). This dose was therefore used in combination with L-NNA for sensitization experiments of gut myoelectric activity. In experiments where NKA-induced no response, pretreatment with L-NNA led to phase II-like activity in 9 of 18 (50%, p<0.05) experiments. Co-administration of SR140333 and SR48968 abolished this effect.

CONCLUSION

NO counteracts the stimulatory effect of tachykinins on small bowel myoelectric activity in the rat. Inhibition of the L-arginine/NO pathway sensitizes the gut to tachykinin-stimulated motor activity.

摘要

未标记

速激肽刺激胃肠道运动，而一氧化氮抑制胃肠道运动。

目的

研究抑制一氧化氮生成是否会使清醒大鼠小肠的肌电活动对阈下剂量的速激肽敏感。

方法

给大鼠植入静脉导管，并在幽门远端5、15和25 cm处放置双极电极用于小肠肌电图检查。使用模式识别评估运动反应。P物质和神经激肽A剂量依赖性地刺激肠道运动，神经激肽A比P物质更有效。因此，选择神经激肽A并在基线条件下以及1 mg kg⁻¹ N（ω）-硝基-L-精氨酸（L-NNA）给药后45 - 60分钟给予，无论是否预先给予300 mg kg⁻¹ L-精氨酸。此外，在给予速激肽受体拮抗剂SR140333（NK1）、SR48968（NK2）和SR142801（NK3）（均为2.5 mg kg⁻¹）之前和之后，研究了神经激肽A与L-NNA联合对肌电活动的影响。

结果

剂量探索研究证实10 pmol kg⁻¹ min⁻¹是阈值剂量，在此剂量下神经激肽A在低比例实验（12%，n = 41）中引起II期样活动。因此，该剂量与L-NNA联合用于肠道肌电活动的致敏实验。在神经激肽A诱导无反应的实验中，L-NNA预处理在18个实验中的9个（50%，p < 0.05）中导致II期样活动。同时给予SR140333和SR48968可消除此效应。