Kiyohara T, Okuno M, Nakanishi T, Shinomura Y, Matsuzawa Y
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Gastroenterology. 1993 May;104(5):1328-36. doi: 10.1016/0016-5085(93)90341-9.
Endothelin may play a significant role in the regulation of gastrointestinal function because it has a variety of biological activities and because endothelin-like immunoreactivity as well as its specific binding sites have been found in the gastrointestinal tract. This study investigated the secretory effect and mechanism of action of endothelin 1 in mammalian large intestine.
Distal colonic segments from Sprague-Dawley rats were stripped of their muscle layers and mounted in Ussing chambers. The effects of endothelin 1 on short-circuit current in rat colonic mucosa were studied in the absence or presence of specific inhibitors. Transmural unidirectional 22Na+ and 36Cl- fluxes and endothelin 1-induced prostacyclin release were also measured.
Serosal addition of endothelin 1 evoked a sustained increase in short-circuit current that was significantly reduced by tetrodotoxin or atropine, and virtually abolished by a selective endothelin A receptor antagonist (BQ-123), furosemide, piroxicam, d,I-verapamil, or removal of serosal calcium. Hexamethonium, amiloride, diphenhydramine, or a specific platelet-activating factor antagonist (CV-6209) did not influence the response to endothelin 1. Endothelin 1 significantly decreased net sodium and net chloride absorption and induced a marked increase in prostacyclin release from the serosal surface of stripped colonic mucosa.
Endothelin 1 has a secretory effect in rat colon. Its action seems to be mediated by cyclo-oxygenase products and enteric nerves via the activation of an endothelin A receptor.
内皮素可能在胃肠功能调节中发挥重要作用，因为它具有多种生物活性，且在胃肠道中已发现内皮素样免疫反应性及其特异性结合位点。本研究调查了内皮素1在哺乳动物大肠中的分泌作用及作用机制。
从Sprague-Dawley大鼠分离出远端结肠段，去除肌层后安装在Ussing槽中。在存在或不存在特异性抑制剂的情况下，研究内皮素1对大鼠结肠黏膜短路电流的影响。还测量了跨膜单向22Na+和36Cl-通量以及内皮素1诱导的前列环素释放。
向浆膜侧添加内皮素1可引起短路电流持续增加，该增加被河豚毒素或阿托品显著降低，而被选择性内皮素A受体拮抗剂（BQ-123）、呋塞米、吡罗昔康、d，l-维拉帕米或去除浆膜钙几乎完全消除。六甲铵、氨氯地平、苯海拉明或特异性血小板活化因子拮抗剂（CV-6209）不影响对内皮素1的反应。内皮素1显著降低钠和氯的净吸收，并诱导从剥离的结肠黏膜浆膜表面释放的前列环素显著增加。
内皮素1在大鼠结肠中具有分泌作用。其作用似乎是通过环氧化酶产物和肠神经，经由内皮素A受体的激活介导的。
