阿托品化猫盆腔神经刺激后结肠激肽释放酶的动员

Mobilization of colonic kallikrein following pelvic nerve stimulation in the atropinized cat.

作者信息

Fasth S, Hulten L, Johnson B J, Nordgren S, Zeitlin I J

出版信息

J Physiol. 1978 Dec;285:471-8. doi: 10.1113/jphysiol.1978.sp012583.

DOI:10.1113/jphysiol.1978.sp012583

PMID:745111

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1281768/

Abstract

Pelvic nerve stimulation (p.n.s.) in cats induces atropine-resistant colonic vasodilatation and colonic contraction. The effects of this on cat colon are mimicked by synthetic bradykinin infusions. The present study examines the effect of p.n.s. on the activation of kallikrein, the kinin-forming enzyme present in colonic tissue and its effects on the plasma kinin system in the atropinized cat.2. Mean level (+/- S.D.) of mucosal kallikrein was found to be about 37 times higher in unstimulated colonic mucosa (300 +/- 100 ng bradykinin equivalents min(-1)g(-1)) than in the underlying muscle (8.2 +/- 6.3 ng bradykinin equiv min(-1)g(-1)).3. After a p.n.s. of 5 min, mean kallikrein level in colonic muscle was 7.3 +/- 3.5 ng bradykinin equiv min(-1)g(-1), which was not significantly different from the control muscle kallikrein. However, there was an 86% fall in mucosal kallikrein to 41.3 +/- 34.7 ng bradykinin equiv min(-1)g(-1) after 5 min p.n.s., indicating a rapid activation and secretion of mucosal kallikrein.4. Secretion of mucosal kallikrein was paralleled by specific depletion of plasma kininogen, the precursor of active kinin in blood draining the colon. The mean plasma kininogen level fell to 79 and 68% of the prestimulated value (3.1 +/- 1.1 S.D. mug bradykinin equiv per ml. plasma) after 5 and 10 min p.n.s. respectively. Total plasma protein and haematocrit remained unaltered excluding non-specific changes due to protein extravasation or haemodilution and indicating utilization of the plasma kinin precursor.5. Following 2 hr p.n.s., raised levels of kallikrein were detected in both colonic muscle (28 +/- 2.0 bradykinin equiv min(-1)g(-1)) and mucosa 434 +/- 118 ng bradykinin equiv min(-1)g(-1)). Preliminary studies using a kallikrein inhibitor indicated that the increased kallikrein levels originated from plasma.6. Direct stimulation of the parasympathetic pelvic nerve in the atropinized cat thus produced activation of the plasma kinin system in the colon and formation of free kinins may be responsible for the mucosal vasodilatation and strong motor contraction which is not blocked by large doses of atropine. The observation that prolonged stimulation causes extravasation of plasma kallikrein, a potential inflammatory mediator, into the tissues may be of clinical significance.

摘要

对猫进行盆腔神经刺激（PNS）可诱发阿托品抵抗性结肠血管舒张和结肠收缩。合成缓激肽输注可模拟其对猫结肠的作用。本研究探讨了PNS对激肽释放酶激活的影响，激肽释放酶是结肠组织中形成激肽的酶，以及其对阿托品化猫血浆激肽系统的影响。
发现未受刺激的结肠黏膜中黏膜激肽释放酶的平均水平（±标准差）（300±100 ng缓激肽当量min⁻¹g⁻¹）比其下方肌肉中的水平（8.2±6.3 ng缓激肽当量min⁻¹g⁻¹）高约37倍。
进行5分钟的PNS后，结肠肌肉中激肽释放酶的平均水平为7.3±3.5 ng缓激肽当量min⁻¹g⁻¹，与对照肌肉激肽释放酶无显著差异。然而，5分钟PNS后，黏膜激肽释放酶下降了86%，至41.3±34.7 ng缓激肽当量min⁻¹g⁻¹，表明黏膜激肽释放酶被快速激活并分泌。
黏膜激肽释放酶的分泌伴随着血浆激肽原的特异性消耗，血浆激肽原是结肠引流血液中活性激肽的前体。分别在5分钟和10分钟PNS后，血浆激肽原的平均水平降至刺激前值（3.1±1.1标准差μg缓激肽当量/ml血浆）的79%和68%。总血浆蛋白和血细胞比容保持不变，排除了由于蛋白质外渗或血液稀释引起的非特异性变化，表明血浆激肽前体被利用。
进行2小时的PNS后，在结肠肌肉（28±2.0缓激肽当量min⁻¹g⁻¹）和黏膜（434±118 ng缓激肽当量min⁻¹g⁻¹）中均检测到激肽释放酶水平升高。使用激肽释放酶抑制剂的初步研究表明，激肽释放酶水平的升高源自血浆。
因此，在阿托品化的猫中直接刺激副交感神经盆腔神经可激活结肠中的血浆激肽系统，游离激肽的形成可能是黏膜血管舒张和强烈运动收缩的原因，而大剂量阿托品不能阻断这种收缩。长时间刺激导致血浆激肽释放酶（一种潜在的炎症介质）外渗到组织中的观察结果可能具有临床意义。