Neurotensin stimulates Cl(-) secretion in human colonic mucosa In vitro: role of adenosine.

Neurotensin stimulates Cl(-) secretion in human colonic mucosa In vitro: role of adenosine.
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神经降压素刺激人结肠粘膜 Cl(-) 分泌体外:腺苷的作用。

DOI:
10.1053/gast.2000.9310
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发表时间:
2000
期刊:
影响因子:
29.4
通讯作者:
Pothoulakis,C
Pothoulakis,C
中科院分区:
医学1区
文献类型:
--
作者:
Riegler,M;Castagliuolo,I;Wang,C;Wlk,M;Sogukoglu,T;Wenzl,E;Matthews,JB;Pothoulakis,C

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背景与目的神经降压肽(neurotensin,NT)在体外刺激动物小肠粘膜Cl−分泌。在这项研究中,我们调查是否NT导致Cl-分泌在人类结肠粘膜和检查这种respons.MethodsHuman粘膜制剂安装在Ussing室的机制暴露于NT。NT诱导反应的药理学表征药物在NT前30分钟应用。(10− 8至10− 6 mol/L)诱导快速、单相、浓度和氯离子依赖性、布美他尼敏感性短路电流(Isc)增加,可被特异性非肽NT受体拮抗剂SR 48692和SR 142948 A抑制,神经阻滞剂河豚毒素和前列腺素合成抑制剂吲哚美辛。肥大细胞稳定剂洛度沙胺和组胺1和2受体拮抗剂吡拉明和雷尼替丁,分别没有显着改变NT诱导的Isc增加。相反,腺苷受体1和2拮抗剂抑制这种分泌反应,而腺苷摄取的促进剂S-(4-硝基苄基)-6-硫代鸟苷和S-(4-硝基苄基)-6-硫代肌苷和腺苷脱氨酶抑制剂脱氧共福霉素加强NT诱导的Isc增加。serenosadenosine诱导的快速,双相,浓度和氯依赖性,布美他尼敏感的Isc increasing.ConclusionsNT刺激氯分泌在人结肠的途径(S)涉及粘膜神经,腺苷,和alphylandins。
Background & AimsPrevious studies indicated that the peptide neurotensin (NT) stimulates Cl−secretion in animal small intestinal mucosa in vitro. In this study, we investigated whether NT causes Cl−secretion in human colonic mucosa and examined the mechanism of this response.MethodsHuman mucosal preparations mounted in Ussing chambers were exposed to NT. Drugs for pharmacologic characterization of NT-induced responses were applied 30 minutes before NT.ResultsSerosal, but not luminal, administration of NT (10−8to 10−6mol/L) induced a rapid, monophasic, concentration- and chloride-dependent, bumetanide-sensitive short-circuit current (Isc) increase that was inhibited by the specific nonpeptide NT receptor antagonists SR 48692 and SR 142948A, the neuronal blocker tetrodotoxin, and the prostaglandin synthesis inhibitor indomethacin. The mast cell stabilizer lodoxamide and the histamine 1 and 2 receptor antagonists pyrilamine and ranitidine, respectively, did not significantly alter NT-induced Isc increase. In contrast, the adenosine receptor 1 and 2 antagonists inhibited this secretory response, whereas the adenosine uptake inhibitorsS -(4-nitrobenzyl)-6-thioguanosine andS -(4-nitrobenzyl)-6-thioinosine and the adenosine deaminase inhibitor deoxycoformycin potentiated NT-induced Isc increase. Serosal adenosine induced a rapid, monophasic, concentration- and chloride-dependent, bumetanide-sensitive Isc increase.ConclusionsNT stimulates chloride secretion in human colon by a pathway(s) involving mucosal nerves, adenosine, and prostaglandins.
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