Faculty Opinions recommendation of Xenin-25 induces anion secretion by activating noncholinergic secretomotor neurons in the rat ileum.

Xenin-25 is a neurotensin-like peptide that is secreted by enteroendocrine cells in the small intestine. Xenin-8 is reported to augment duodenal anion secretion by activating afferent neural pathways. The intrinsic neuronal circuits mediating the xenin-25-induced anion secretion were characterized using the Ussing-chambered, mucosa-submucosa preparation from the rat ileum. Serosal application of xenin-25 increased the short-circuit current in a concentration-dependent manner. The responses were abolished by the combination of Cl−-free and [Formula: see text]-free solutions. The responses were almost completely blocked by TTX (10−6 M) but not by atropine (10−5 M) or hexamethonium (10−4 M). The selective antagonists for neurotensin receptor 1 (NTSR1), neurokinin 1 (NK1), vasoactive intestinal polypeptide (VIP) receptors 1 and 2 (VPAC1 and VPAC2, respectively), and capsaicin, but not 5-hydroxyltryptamine receptors 3 and 4 (5-HT3 and 5-HT4), NTSR2, and A803467, inhibited the responses to xenin-25. The expression of VIP receptors ( Vipr) in rat ileum was examined using RT-PCR. The Vipr1 PCR products were detected in the submucosal plexus and mucosa. Immunohistochemical staining showed the colocalization of NTSR1 and NK1 with substance P (SP)- and calbindin-immunoreactive neurons in the submucosal plexus, respectively. In addition, NK1 was colocalized with noncholinergic VIP secretomotor neurons. Based on the results from the present study, xenin-25-induced Cl−/[Formula: see text] secretion is involved in NTSR1 activation on intrinsic and extrinsic afferent neurons, followed by the release of SP and subsequent activation of NK1 expressed on noncholinergic VIP secretomotor neurons. Finally, the secreted VIP may activate VPAC1 on epithelial cells to induce Cl−/[Formula: see text] secretion in the rat ileum. Activation of noncholinergic VIP secretomotor neurons by intrinsic primary afferent neurons and extrinsic afferent neurons by postprandially released xenin-25 may account for most of the neurogenic secretory response induced by xenin-25. NEW & NOTEWORTHY This study is the first to investigate the intrinsic neuronal circuit responsible for xenin-25-induced anion secretion in the rat small intestine. We have found that nutrient-stimulated xenin-25 release may activate noncholinergic vasoactive intestinal polypeptide (VIP) secretomotor neurons to promote Cl−/[Formula: see text] secretion through the activation of VIP receptor 1 on epithelial cells. Moreover, the xenin-25-induced secretory responses are mainly linked with intrinsic primary afferent neurons, which are involved in the activation of neurotensin receptor 1 and neurokinin 1 receptor.

Download Full-text

Zinc inhibits cAMP-stimulated Cl secretion via basolateral K-channel blockade in rat ileum

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00441.2004 ◽

2005 ◽

Vol 288 (5) ◽

pp. G956-G963 ◽

Cited By ~ 56

Author(s):

Kazi Mirajul Hoque ◽

Vazhaikkurichi M. Rajendran ◽

Henry J. Binder

Keyword(s):

Short Circuit ◽

Basolateral Membrane ◽

Short Circuit Current ◽

K Channel ◽

Isolated Cells ◽

Rat Ileum ◽

Anion Secretion ◽

Cl Secretion ◽

Ion Absorption ◽

Isotonic Buffer

Zn, an essential micronutrient and second most abundant trace element in cell and tissues, reduces stool output when administered to children with acute diarrhea. The mechanism by which Zn improves diarrhea is not known but could result from stimulating Na absorption and/or inhibiting anion secretion. The aim of this study was to investigate the direct effect of Zn on intestinal epithelial ion absorption and secretion. Rat ileum was partially stripped of serosal and muscle layers, and the mucosa was mounted in lucite chambers. Potential difference and short-circuit current were measured by conventional current-voltage clamp method.86Rb efflux and uptake were assessed for serosal K channel and Na-K-2Cl cotransport activity, respectively. Efflux experiments were performed in isolated cells preloaded with86Rb in the presence of ouabain and bumetanide, whereas uptake experiments were performed in low-Cl isotonic buffer containing Ba and ouabain. Neither mucosal nor serosal Zn affected glucose-stimulated Na absorption. In contrast, forskolin-induced Cl secretion was markedly reduced by serosal but not mucosal addition of Zn. Zn also substantially reversed the increase in Cl secretion induced by 8-bromoadenosine 3′,5′-cyclic monophosphate (8-BrcAMP) with half-maximal inhibitory concentration of 0.43 mM. In contrast, serosal Zn did not alter Cl secretion stimulated by carbachol, a Ca-dependent agonist. Zn inhibited 8-BrcAMP-stimulated86Rb efflux but not carbachol-stimulated86Rb efflux. Zn had no effect on bumetanide-sensitive86Rb uptake, Na-K-ATPase, or CFTR. We conclude from these studies that Zn inhibits cAMP-induced Cl secretion by blocking basolateral membrane K channels.

Download Full-text

Angtensin II elicits a cAMP-dependent intestinal anion secretion by stimulating PGE2 release through AT1 subtype receptors in rat ileum

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2017.10.052 ◽

2017 ◽

Vol 494 (1-2) ◽

pp. 207-212 ◽

Cited By ~ 1

Author(s):

Ling Xiao ◽

Hong-Wei Liu ◽

Hong Di ◽

Li-Xin Chen ◽

Qing Zhou ◽

...

Keyword(s):

Rat Ileum ◽

Anion Secretion ◽

Pge2 Release

Download Full-text

Minimum biological domain of xenin-25 required to induce anion secretion in the rat ileum

Peptides ◽

10.1016/j.peptides.2021.170680 ◽

2021 ◽

pp. 170680

Author(s):

Yuko Kuwahara ◽

Kohei Takahashi ◽

Miho Akai ◽

Ikuo Kato ◽

Takaharu Kozakai ◽

...

Keyword(s):

Rat Ileum ◽

Anion Secretion ◽

Biological Domain

Download Full-text

Faculty Opinions recommendation of Differential roles of NHERF1, NHERF2, and PDZK1 in regulating CFTR-mediated intestinal anion secretion in mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1157974.618054 ◽

2009 ◽

Author(s):

Kim Barrett

Keyword(s):

Anion Secretion

Download Full-text

Restoration of intestinal mucosal in Euphorbia kansui-treated severe acute pancreatitis rats is based on HMGB1/MFG-E8 expression

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666201218130440 ◽

2020 ◽

Vol 21 ◽

Author(s):

Chengjiang Qiu ◽

Kairui Liu ◽

Xuguang Li ◽

Weirun Chen ◽

Sheng Zhang ◽

...

Keyword(s):

Acute Pancreatitis ◽

Severe Acute Pancreatitis ◽

Serum Amylase ◽

Intestinal Barrier ◽

Enzyme Linked Immunosorbent Assay ◽

Inflammatory Factor ◽

Apoptotic Cells ◽

Rat Ileum ◽

Plasma Endotoxin ◽

Euphorbia Kansui

Background: The pathogenesis of severe acute pancreatitis (SAP) is mediated substantially by dysfunctions in the intestinal barrier. Euphorbia kansui (EK) is a medicinal plant used widely in traditional Chinese medicine to treat inflammation; however, its efficacy and mechanism of action in SAP treatment is not yet well understood. Objective: To investigate the role of EK in intestinal barrier tissue repair and in the pathogenesis and development of SAP. Methods: The rat SAP model was established by a retrograde injection of sodium taurocholate into the pancreatic bile duct. The SAP model group and the SAP + EK treatment groups were divided into 6 subgroups according to timing: 2, 6, 12, 24, 48, or 72 h after inducing SAP. The progression of the SAP rats and of the rats receiving the EK treatment was evaluated using the ascites volume, serum amylase and plasma endotoxin levels, and histological grading of intestinal mucosal damage. In addition, serum inflammatory factor contents were measured using enzyme-linked immunosorbent assay (ELISA) tests and apoptotic cells in damaged ileum tissue were detected using TUNEL staining. Apoptosis markers and other signaling proteins in intestinal mucosal cells were detected by immunohistochemical assays and then validated by combining these data with quantitative polymerase chain reactions and western blotting. Results: Compared with the results of the SAP model rats, the results of the rats that received EK treatment demonstrated that EK could effectively reduce the ascites volume and serum amylase and plasma endotoxin levels. EK treatment also greatly reduced the abnormal intestinal morphological alterations in the rat SAP model and significantly downregulated the serum contents of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. EK treatment inhibited the elevation of capapse-3, inhibited the decrease of the Bcl-2 protein, and decreased the number of apoptotic cells in rat ileum tissue. Finally, EK treatment abrogated the increase of HMGB1 and the suppression of MFG-E8 protein expression in the SAP + EK rat ileum tissue. Conclusion: EK suppresses SAP pathogenesis by restoring intestinal barrier function and modulating the HMGB1/MFG-E8 signaling axis.

Download Full-text