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首页> 外文期刊>American Journal of Physiology >Stimulation of apical Cl/HCO(OH) exchanger, SLC26A3 by neuropeptide Y is lipid raft dependent.
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Stimulation of apical Cl/HCO(OH) exchanger, SLC26A3 by neuropeptide Y is lipid raft dependent.

机译：神经肽Y刺激顶端Cl / HCO（OH）交换剂SLC26A3是脂质筏依赖性的。

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Neuropeptide Y (NPY), an important proabsorptive hormone of the gastrointestinal tract has been shown to inhibit chloride secretion and stimulate NaCl absorption. However, mechanisms underlying the proabsorptive effects of NPY are not fully understood. The present studies were designed to examine the direct effects of NPY on apical Cl/HCO(OH) exchange activity and the underlying mechanisms involved utilizing Caco2 cells. Our results showed that NPY (100 nM, 30 min) significantly increased Cl/HCO(OH) exchange activity ( approximately 2-fold). Selective NPY/Y1 or Y2 receptor agonists mimicked the effects of NPY. NPY-mediated stimulation of Cl/HCO(OH) exchange activity involved the ERK1/2 MAP kinase-dependent pathway. Cell surface biotinylation studies showed that NPY does not alter DRA (apical Cl/HCO(OH) exchanger) surface expression, ruling out the involvement of membrane trafficking events. Interestingly, DRA was found to be predominantly expressed in the detergent-insoluble (DI) and low-density fractions (LDF) of human colonic apical membrane vesicles (AMVs) representing lipid rafts. Depletion of membrane cholesterol by methyl-beta-cyclodextrin (MbetaCD, 10 mM, 1 h) remarkably decreased DRA expression in the DI fractions. Similar results were obtained in Triton-X 100-treated Caco2 plasma membranes. DRA association with lipid rafts in the DI and LDF fractions of Caco2 cells was significantly enhanced ( approximately 45%) by NPY compared with control. MbetaCD significantly decreased Cl/HCO(OH) exchange activity in Caco2 cells as measured by DIDS- or niflumic acid-sensitive (3)Cl uptake ( approximately 50%). Our results demonstrate that NPY modulates Cl/HCO(OH) exchange activity by enhancing the association of DRA with lipid rafts, thereby resulting in an increase in Cl/HCO(OH) exchange activity. Our findings suggest that the alteration in the association of DRA with lipid rafts may contribute to the proabsorptive effects of NPY in the human intestine.
机译：神经肽Y（NPY）是胃肠道的一种重要的促吸收激素，已显示出抑制氯化物分泌和刺激NaCl吸收的作用。但是，尚未完全了解NPY的吸收作用的潜在机制。本研究旨在检查NPY对顶端Cl / HCO（OH）交换活性的直接影响以及涉及利用Caco2细胞的潜在机制。我们的结果表明，NPY（100 nM，30分钟）显着增加了Cl / HCO（OH）交换活性（约2倍）。选择性的NPY / Y1或Y2受体激动剂模仿了NPY的作用。 NPY介导的Cl / HCO（OH）交换活性的刺激涉及ERK1 / 2 MAP激酶依赖性途径。细胞表面生物素化研究表明，NPY不会改变DRA（顶端Cl / HCO（OH）交换子）表面表达，从而排除了膜运输事件的参与。有趣的是，发现DRA主要在代表脂质筏的人结肠顶膜囊泡（AMV）的去污剂不溶性（DI）和低密度级分（LDF）中表达。甲基-β-环糊精（MbetaCD，10 mM，1 h）消耗膜胆固醇显着降低了DI级分中的DRA表达。在Triton-X 100处理的Caco2质膜上获得了相似的结果。与对照组相比，NPY显着增强了Caco2细胞DI和LDF组分中DRA与脂质筏的相关性（约45％）。 MbetaCD显着降低了Caco2细胞中的Cl / HCO（OH）交换活性，这是通过DIDS或尼氟酸敏感的（3）Cl吸收量测得的（约50％）。我们的结果表明，NPY通过增强DRA与脂质筏的结合来调节Cl / HCO（OH）交换活性，从而导致Cl / HCO（OH）交换活性的增加。我们的发现表明，DRA与脂筏的关联改变可能有助于NPY在人肠中的吸收作用。

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