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.
Highlights
Glutamine (Gln) is the most abundant free amino acid (AA) in mammalian plasma and is traditionally considered a non—essential amino acid
Since the store-operated Ca2+ entry (SOCE) is a well-established mechanism to regulate the Ca2+-dependent functions in IEC, including jejunal glucose absorption (Zhang et al, 2021),we examined whether the SOCE mechanism regulates ileal Gln-induced short-circuit current (Isc) and started with GdCl3, a commonly used SOCE blocker
Distribution and functional specificity of intestinal Gln transporters, our data suggest that Na+/Gln cotransporters (NGcT) (B0AT1) may play a major role in this process, but the other transporters cannot be ruled out completely (Broer and Fairweather 2019; Chen et al, 2020)
Summary
Glutamine (Gln) is the most abundant free amino acid (AA) in mammalian plasma and is traditionally considered a non—essential amino acid. During periods of increased intestinal stress, Gln can stimulate intestinal nutrient absorption while maintaining mucosal barrier function and promoting mucosal growth (Chen et al, 2018; Li et al, 2019). Investigation on the regulation of Gln uptake will further promote our understanding of its role in GI health and therapeutic application in GI diseases. Ca2+ Regulation of Ileal Glutamine (25 mM)-stimulated Isc of the duodenum, proximal jejunum, and distal ileum.
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