Ca(2+)-Permeable Channels/Ca(2+) Signaling in the Regulation of Ileal Na(+)/Gln Co-Transport in Mice.

Ca(2+)-Permeable Channels/Ca(2+) Signaling in the Regulation of Ileal Na(+)/Gln Co-Transport in Mice.
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Ca2 通透通道/Ca2 信号传导在小鼠回肠 Na/Gln 协同转运调节中的作用

DOI:
10.3389/fphar.2022.816133
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发表时间:
2022
影响因子:
5.6
通讯作者:
Lü M
Lü M
中科院分区:
医学2区
文献类型:
--
作者:
Chu F;Wan H;Xiao W;Dong H;Lü M

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口服谷氨酰胺(GLN)已被广泛应用于胃肠道(GI)的临床实践,但目前尚不清楚钙离子是否调节肠道谷氨酰胺的转运,尽管两者都是哺乳动物的必需营养物质。在没有或存在选择性离子通道和转运蛋白激活剂或阻断剂的情况下,用小室测定谷氨酰胺(25 MM)通过Na+/Gln共转运体在小肠诱导的Isc。腔内应用谷氨酰胺而不是浆膜应用谷氨酰胺可引起明显的肠梗阻,尤其是在回肠远端。降低钠离子浓度可使谷氨酰胺诱导的回肠Isc几乎完全消失,但不参与钙敏感受体(CaSR)的激活。从回肠腔和浆膜两侧清除钙离子可显著降低Gln-I sc。阻断电压门控性钙通道(VGCC)或三磷酸肌醇受体(IP3R)和兰尼定受体(RyR)释放内质网(ER)均可减弱Gln诱导的回肠Isc,同样,阻断浆膜Ca~(2+)内流(SOCE)、TRPV1/2通道和Na+/Ca~(2+)交换器(NCX)可减弱GLN诱导的回肠Isc。相反,激活TRPV1/2通道可增强Gln诱导的回肠Isc。我们认为,钙信号在肠道谷氨酸氨基转移中起关键作用,多个质膜钙通透性通道和转运体在这一过程中发挥作用。Ca~(2+)对回肠Na~+/Gln转运的调节扩大了我们对肠道养分摄取的理解,可能对胃肠道健康和疾病有重要意义。
Oral glutamine (Gln) has been widely used in gastrointestinal (GI) clinical practice, but it is unclear if Ca2+ regulates intestinal Gln transport, although both of them are essential nutrients for mammals. Chambers were used to determine Gln (25 mM)-induced I sc through Na+/Gln co-transporters in the small intestine in the absence or the presence of selective activators or blockers of ion channels and transporters. Luminal but not serosal application of Gln induced marked intestinal I sc , especially in the distal ileum. Lowering luminal Na+ almost abolished the Gln-induced ileal I sc , in which the calcium-sensitive receptor (CaSR) activation were not involved. Ca2+ removal from both luminal and serosal sides of the ileum significantly reduced Gln- I sc . Blocking either luminal Ca2+ entry via the voltage-gated calcium channels (VGCC) or endoplasmic reticulum (ER) release via inositol 1,4,5-triphosphate receptor (IP3R) and ryanodine receptor (RyR) attenuated the Gln-induced ileal I sc , Likewise, blocking serosal Ca2+ entry via the store-operated Ca2+ entry (SOCE), TRPV1/2 channels, and Na+/Ca2+ exchangers (NCX) attenuated the Gln-induced ileal I sc . In contrast, activating TRPV1/2 channels enhanced the Gln-induced ileal I sc . We concluded that Ca2+ signaling is critical for intestinal Gln transport, and multiple plasma membrane Ca2+-permeable channels and transporters play roles in this process. The Ca2+ regulation of ileal Na+/Gln transport expands our understanding of intestinal nutrient uptake and may be significant in GI health and disease.
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