Amino acids in the rat intestinal lumen regulate their own absorption from a distant intestinal site

Mourad, Fadi H.; Barada, Kassem; Khoury, Carmen I.; Hamdi, Tamim; Saadé, Nayef E.; Nassar, Camille F.

doi:10.1152/ajpgi.00100.2009

Cited by 15 publications

(7 citation statements)

References 51 publications

(55 reference statements)

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“…There is limited overlap of ACE2 and B 0 AT1 expression in the kidney, where the transporter is mainly associated with collectrin [55]. Recently, alterations in substrate affinity for alanine, a major B 0 AT1 substrate, were also demonstrated over widespread sections of rat small intestine incubated in more proximal sections with the same amino acids that displayed affinity alterations [56]. …”

Section: Discussionmentioning

confidence: 99%

Intestinal peptidases form functional complexes with the neutral amino acid transporter B0AT1

Fairweather

Bröer

O’Mara

et al. 2012

Biochemical Journal

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The brush-border membrane of the small intestine and kidney proximal tubule are the major sites for the absorption and re-absorption of nutrients in the body respectively. Transport of amino acids is mediated through the action of numerous secondary active transporters. In the mouse, neutral amino acids are transported by B0AT1 [broad neutral (0) amino acid transporter 1; SLC6A19 (solute carrier family 6 member 19)] in the intestine and by B0AT1 and B0AT3 (SLC6A18) in the kidney. Immunoprecipitation and Blue native electrophoresis of intestinal brush-border membrane proteins revealed that B0AT1 forms complexes with two peptidases, APN (aminopeptidase N/CD13) and ACE2 (angiotensin-converting enzyme 2). Physiological characterization of B0AT1 expressed together with these peptidases in Xenopus laevis oocytes revealed that APN increased the substrate affinity of the transporter up to 2.5-fold and also increased its surface expression (Vmax). Peptide competition experiments, in silico modelling and site-directed mutagenesis of APN suggest that the catalytic site of the peptidase is involved in the observed changes of B0AT1 apparent substrate affinity, possibly by increasing the local substrate concentration. These results provide evidence for the existence of B0AT1-containing digestive complexes in the brush-border membrane, interacting differentially with various peptidases, and responding to the dynamic needs of nutrient absorption in the intestine and kidney.

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Section: Discussionmentioning

confidence: 99%

Intestinal peptidases form functional complexes with the neutral amino acid transporter B0AT1

Fairweather

Bröer

O’Mara

et al. 2012

Biochemical Journal

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“…It is now well-established that CGRP regulates blood pressure (Brain and Grant, 2004), is associated with the onset of migraines when at high levels (Olesen, 2011a,b), promotes the maintenance of mucosal integrity in the gastro-intestinal tract (GIT) (Szolcsanyi and Bartho, 2001), aids stem cell growth and maintenance in vitro (Dong et al, 2010) and modulates keratinocyte growth (Roggenkamp et al, 2013). CGRP plays a role in facilitating the absorption of intraluminal amino acids across the distal parts of the intestines (Mourad et al, 2009). In the lungs and elsewhere, CGRP promotes wound healing (Zhou et al, 2013).…”

Section: Physiological Role For Cgrpmentioning

confidence: 99%

Calcitonin gene-related peptide is a key neurotransmitter in the neuro-immune axis

2014

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The question of how the neural and immune systems interact in host defense is important, integrating a system that senses the whole body with one that protects. Understanding the mechanisms and routes of control could produce novel and powerful ways of promoting and enhancing normal functions as well as preventing or treating abnormal functions. Fragmentation of biological research into specialities has resulted in some failures in recognizing and understanding interactions across different systems and this is most striking across immunology, hematology, and neuroscience. This reductionist approach does not allow understanding of the in vivo orchestrated response generated through integration of all systems. However, many factors make the understanding of multisystem cross-talk in response to a threat difficult, for instance the nervous and immune systems share communication molecules and receptors for a wide range of physiological signals. But, it is clear that physical, hard-wired connections exist between the two systems, with the key link involving sensory, unmyelinated nerve fibers (c fibers) containing the neuropeptide calcitonin gene-related peptide (CGRP), and modified macrophages, mast cells and other immune and host defense cells in various locations throughout the body. In this review we will therefore focus on the induction of CGRP and its key role in the neuroimmune axis.

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“…Also a glutamine-enriched diet was shown to increase glutamine uptake in jejunal bbmv from rats compared to a control diet [ 30 ]. Some experiments in which high concentrations of amino acids were administered in small intestinal loops of rats also suggested the possibility of a short-term (20 min) amino acid-induced regulation of amino acid absorption [ 31 ]. Rodents are nocturnal animals with their active phase in the night.…”

Section: Introductionmentioning

confidence: 99%

Expression and regulation of the neutral amino acid transporter B0AT1 in rat small intestine

et al. 2017

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Absorption of neutral amino acids across the luminal membrane of intestinal enterocytes is mediated by the broad neutral amino acid transporter B 0 AT1 (SLC6A19). Its intestinal expression depends on co-expression of the membrane-anchored peptidase angiotensin converting enzyme 2 (ACE2) and is additionally enhanced by aminopeptidase N (CD13). We investigated in this study the expression of B 0 AT1 and its auxiliary peptidases as well as its transport function along the rat small intestine. Additionally, we tested its possible shortand long-term regulation by dietary proteins and amino acids. We showed by immunofluorescence that B 0 AT1, ACE2 and CD13 co-localize on the luminal membrane of small intestinal villi and by Western blotting that their protein expression increases in distal direction. Furthermore, we observed an elevated transport activity of the neutral amino acid L-isoleucine during the nocturnal active phase compared to the inactive one. protein expression under amino acid-supplemented diet in the proximal section but not in the distal one and for ACE2 protein expression a reverse localization of the effect. Dietary regulation for CD13 protein expression was not as distinct as for the two other proteins. Ring uptake experiments showed a tendency for increased L-isoleucine uptake under amino acid-supplemented diet and in vivo L-isoleucine absorption was more efficient under high protein and amino acid-supplemented diet. Additionally, plasma levels of branched-chain amino acids were elevated under high protein and amino acid diet. Taken together, our experiments did not reveal an acute amino acid-induced regulation of B 0 AT1 but revealed a chronic dietary adaptation mainly restricted to the proximal segment of the small intestine.

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Amino acids in the rat intestinal lumen regulate their own absorption from a distant intestinal site

Cited by 15 publications

References 51 publications

Intestinal peptidases form functional complexes with the neutral amino acid transporter B0AT1

Intestinal peptidases form functional complexes with the neutral amino acid transporter B0AT1

Calcitonin gene-related peptide is a key neurotransmitter in the neuro-immune axis

Expression and regulation of the neutral amino acid transporter B0AT1 in rat small intestine

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