期刊
EXPERIMENTAL CELL RESEARCH
卷 315, 期 17, 页码 3028-3035出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2009.06.005
关键词
Anion secretion; Short-circuit current; Colonic epithelia; Co-immunoprecipitation
资金
- Canadian Institutes of Health Research
- Canadian Cystic Fibrosis Foundation
Cholesterol affects diverse biological processes, in many cases by modulating the function of integral membrane proteins. In this study we have investigated the role of cholesterol in the adenosine-dependent regulation of ion transport in colonic epithelial cells. We observed that methyl-beta-cyclodextrin (M beta CD), a cholesterol-sequestering molecule, enhanced adenosine A(2A) receptor-activated transepithelial short circuit Current (I-sc), but only from the basolateral side. Cholesterol is a major constituent of membrane microdomains, called lipid rafts that also contain sphingolipids. However, studies with the sphingomyelin-degrading enzyme, sphingomyelinase, and the cholesterol-binding agent, filipin, indicated that the change in the level of cholesterol alone was sufficient to control the adenosine-modulated I-sc. Cholesterol depletion had a major effect on the functional selectivity of A(2A) receptors. Under control conditions, adenosine activated I-sc more potently than the specific A(2A) agonist, CGS-21680, and the current was inhibited by XE991, an inhibitor of cAMP-dependent K+ channels. Following cholesterol depletion, CGS-21680 activated I-sc more potently than adenosine, and the current was inhibited by clotrimazole, an inhibitor of Ca2+-activated K+ (IK1) channels. Co-iminunoprecipitation experiments revealed that A(2A) receptors associate with IK1 channels following cholesterol depletion. These results suggest that cholesterol content in colonic epithelia affects adenosine-mediated anion secretion by controlling agonist-selective signaling. (C) 2009 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据