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• W4224441320 endingPage "102248" @default.
• W4224441320 startingPage "102248" @default.
• W4224441320 abstract "Growing evidence indicates that visceral hypersensitivity and impaired gut barrier play an important role in the pathophysiology of irritable bowel syndrome (IBS). In animal models, these changes are known to be mediated via corticotropin-releasing factor (CRF)-Toll like receptor 4 (TLR4)-proinflammatory cytokine signaling. Apelin, an endogenous ligand of APJ, was reported to modulate CRF-induced enhanced colonic motility. In this context, we hypothesized that apelin also modulates visceral sensation and gut barrier, and tested this hypothesis. We measured visceral pain threshold in response to colonic balloon distention by abdominal muscle contractions assessed by electromyogram in rats. Colonic permeability was estimated by quantifying the absorbed Evans blue in colonic tissue. Intraperitoneal (ip) administration of [Ala13]-apelin-13, an APJ antagonist, blocked lipopolysaccharide (LPS)- or CRF-induced visceral hypersensitivity and colonic hyperpermeability (IBS model) in a dose-response manner. These inhibitory effects were blocked by compound C, an AMPK inhibitor, NG-nitro-L-arginine methyl ester, a nitric oxide (NO) synthesis inhibitor or naloxone in the LPS model. On the other hand, ip [Pyr1]-apelin-13, an APJ agonist, caused visceral hypersensitivity and colonic hyperpermeability, and these effects were reversed by astressin, a CRF receptor antagonist, TAK-242, a TLR4 antagonist or anakinra, an interleukin-1 receptor antagonist. APJ system modulated CRF-TLR4-proinflammatory cytokine signaling to cause visceral hypersensitivity and colonic hyperpermeability. APJ antagonist blocked these GI changes in IBS models, which were mediated via AMPK, NO and opioid signaling. Apelin may contribute to the IBS pathophysiology, and the inhibition of apelinergic signaling may be a promising therapeutic option for IBS." @default.
• W4224441320 created "2022-04-27" @default.
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• W4224441320 date "2022-08-01" @default.
• W4224441320 modified "2023-10-15" @default.
• W4224441320 title "Peripheral apelin mediates visceral hypersensitivity and impaired gut barrier in a rat irritable bowel syndrome model" @default.
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• W4224441320 doi "https://doi.org/10.1016/j.npep.2022.102248" @default.
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