1 Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) differentially activate three Y receptors (Y(1), Y(2) and Y(4)) in mouse and human isolated colon. 2 The aim of this study was to characterise Y(2) receptor-mediated responses in colon mucosa and longitudinal smooth muscle preparations from wild type (Y(2)+/+) and knockout (Y(2)-/-) mice and to compare the former with human mucosal Y agonist responses. Inhibition of mucosal short-circuit current and increases in muscle tone were monitored in colonic tissues from Y(2)+/+ and Y(2)-/- mice+/-Y(1) ((R)-N-[[4-(aminocarbonylaminomethyl)phenyl)methyl]-N(2)-(diphenylacetyl)-argininamide-trifluoroacetate (BIBO3304) or Y(2) (S)-N(2)-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6H)-oxodibenz[b,e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl]cyclopentyl]acetyl]-N-[2-[1,2-dihydro-3,5(4H)-dioxo-1,2-diphenyl-3H-1,2,4-triazol-4-yl]ethyl]-argininamide (BIIE0246) antagonists. 3 Predictably, Y(2)-/- tissues were insensitive to Y(2)-preferred agonist PYY(3-36) (=100 nM), but unexpectedly Y(4)-preferred PP responses were right-shifted probably as a consequence of elevated circulating PP levels, particularly in male Y(2)-/- mice (Sainsbury et al., 2002). 4 BIBO3304 and BIIE0246 elevated mucosal ion transport, indicating blockade of inhibitory mucosal tone in Y(2)+/+ tissue. While BIBO3304 effects were unchanged, those to BIIE0246 were absent in Y(2)-/- mucosae. Neither antagonist altered muscle tone; however, BIIE0246 blocked NPY and PYY(3-36) increases in Y(2)+/+ basal tone. BIBO3304 abolished residual Y(1)-mediated NPY responses in Y(2)-/- smooth muscle. 5 Tetrodotoxin significantly reduced BIIE0246 and PYY(3-36) effects in Y(2)+/+ mouse and human mucosae, but had no effect upon Y-agonist contractile responses, indicating that Y(2) receptors are located on submucosal, but not myenteric neurones. 6 Tonic activation of submucosal Y(2) receptors by endogenous NPY, PYY or PYY(3-36) could indirectly reduce mucosal ion transport in murine and human colon, while direct activation of Y(2) receptors on longitudinal muscle results in contraction.
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http://dx.doi.org/10.1038/sj.bjp.0705298 | DOI Listing |
Gut Microbes
December 2025
Department of Oncology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
() exhibits aberrant changes in patients with colitis, and it has been reported to dominate the colonic mucosal immune response. Here, we found that PMA1 expression was significantly increased in from patients with IBD compared to that in healthy controls. A Crispr-Cas9-based fungal strain editing system was then used to knock out PMA1 expression in .
View Article and Find Full Text PDFJID Innov
March 2025
Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
With the goal of studying skin wound healing and testing new drug treatments to enhance wound healing in rodent models, there is a clear need for improved splinting techniques to increase surgical efficiency and support routine wound monitoring. Splinted wound healing models humanize wound healing in rodents to prevent contraction and instead heal through granulation tissue deposition, increasing the relevance to human wound healing. Current technologies require suturing and heavy wrapping, leading to splint failure and cumbersome monitoring of the wound.
View Article and Find Full Text PDFResearch (Wash D C)
January 2025
Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
Sepsis-associated encephalopathy (SAE) is a severe and frequent septic complication, characterized by neuronal damage as key pathological features. The astrocyte-microglia crosstalk in the central nervous system (CNS) plays important roles in various neurological diseases. However, how astrocytes interact with microglia to regulate neuronal injury in SAE is poorly defined.
View Article and Find Full Text PDFBMJ Oncol
November 2023
Rowett Institute, University of Aberdeen, Aberdeen, UK.
Cancer remains one of the leading causes of death worldwide, despite advances in treatments such as surgery, chemotherapy, radiotherapy and immunotherapy. The role of the gut microbiota in human health and disease, particularly in relation to cancer incidence and treatment response, has gained increasing attention. Emerging evidence suggests that dietary fibre, including prebiotics, can modulate the gut microbiota and influence antitumour effects.
View Article and Find Full Text PDFAnn Neurosci
January 2025
Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India.
Background: Stroke is one of the leading causes of death and long-term adult disability worldwide. Stroke causes neurodegeneration and impairs synaptic function. Understanding the role of synaptic proteins and associated signalling pathways in stroke pathology could offer insights into therapeutic approaches as well as improving rehabilitation-related treatment regimes.
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