AUTHOR=Chu Fenglan , Wan Hanxing , Xiao Weidong , Dong Hui , Lü Muhan TITLE=Ca2+-Permeable Channels/Ca2+ Signaling in the Regulation of Ileal Na+/Gln Co-Transport in Mice JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.816133 DOI=10.3389/fphar.2022.816133 ISSN=1663-9812 ABSTRACT=

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.