Cholesterol-dependent regulation of adenosine A2A receptor-mediated anion secretion in colon epithelial cells
| Autor: | Drew Nahirney, Marek Duszyk, Rebecca S. Lam |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Receptor
Adenosine A2A Colon Caveolin 1 Adenosine-5'-(N-ethylcarboxamide) Biology Filipin Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Homeostasis Intestinal Mucosa Receptor Lipid raft Ion transporter 030304 developmental biology Mice Knockout 0303 health sciences Cholesterol Cell Membrane Cell Biology Adenosine Sphingolipid 3. Good health Cell biology Mice Inbred C57BL Kinetics chemistry lipids (amino acids peptides and proteins) Sphingomyelin 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Experimental Cell Research. 315:3028-3035 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2009.06.005 |
| Popis: | 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 (MbetaCD), 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 Ca(2+)-activated K(+) (IK1) channels. Co-immunoprecipitation 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. |
| Databáze: | OpenAIRE |
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