Riegler M, Castagliuolo I, Wang C, Wlk M, Sogukoglu T, Wenzl E, Matthews J B, Pothoulakis C
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Gastroenterology. 2000 Aug;119(2):348-57. doi: 10.1053/gast.2000.9310.
BACKGROUND & AIMS: Previous 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.
Human mucosal preparations mounted in Ussing chambers were exposed to NT. Drugs for pharmacologic characterization of NT-induced responses were applied 30 minutes before NT.
Serosal, but not luminal, administration of NT (10(-8) to 10(-6) mol/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 inhibitors S-(4-nitrobenzyl)-6-thioguanosine and S-(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.
NT stimulates chloride secretion in human colon by a pathway(s) involving mucosal nerves, adenosine, and prostaglandins.
以往研究表明，肽神经降压素（NT）在体外可刺激动物小肠黏膜的氯离子分泌。在本研究中，我们调查了NT是否会引起人结肠黏膜的氯离子分泌，并研究了这种反应的机制。
将安装在尤斯灌流小室中的人黏膜制剂暴露于NT。在给予NT前30分钟应用药物对NT诱导的反应进行药理学特征分析。
浆膜面而非肠腔面给予NT（10⁻⁸至10⁻⁶mol/L）可诱导快速、单相、浓度和氯离子依赖性、布美他尼敏感的短路电流（Isc）增加，该增加被特异性非肽类NT受体拮抗剂SR 48692和SR 142948A、神经元阻滞剂河豚毒素以及前列腺素合成抑制剂吲哚美辛所抑制。肥大细胞稳定剂洛度沙胺以及组胺1和2受体拮抗剂吡苄明和雷尼替丁分别未显著改变NT诱导的Isc增加。相反，腺苷受体1和2拮抗剂抑制了这种分泌反应，而腺苷摄取抑制剂S-(4-硝基苄基)-6-硫代鸟苷和S-(4-硝基苄基)-6-硫代肌苷以及腺苷脱氨酶抑制剂脱氧助间型霉素增强了NT诱导的Isc增加。浆膜面给予腺苷可诱导快速、单相、浓度和氯离子依赖性、布美他尼敏感的Isc增加。
NT通过涉及黏膜神经、腺苷和前列腺素的途径刺激人结肠的氯离子分泌。
Zotero 插件