Immunocytochemical Localization of the NPY/PYY Y1 Receptor in Enteric Neurons, Endothelial Cells, and Endocrine-like Cells of the Rat Intestinal Tract

Jackerott, Malene; Larsson, Lars‐Inge

doi:10.1177/002215549704501207

Cited by 50 publications

(40 citation statements)

References 52 publications

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“…The cellular sites of Y1 receptor activation could involve the myenteric and submucosal nerve cell bodies and endothelial and endocrine-like cells in the colon, because all of these cell types have been described to express Y1 receptors (7,11,15,31). In agreement with previous experimental data (1, 2), we observed increased NPY immunoreactivity in both Y1 Ϫ/Ϫ and Y1 ϩ/ϩ mice receiving 5% DSS, and thus this increase occurs independent of the Y1 receptor.…”

Section: And Y1supporting

confidence: 91%

Attenuation of acute experimental colitis by preventing NPY Y1 receptor signaling

Hassani

Lucas

Rozell

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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Neuropeptide Y (NPY), a 36-amino acid peptide, is widely expressed in the central and peripheral nervous system. NPY is involved in the regulation of several physiological processes, including energy balance, food intake, and nociception. Recently, we showed that activation of the NPY Y1 receptor is required for cutaneous neurogenic inflammation. Because neurogenic inflammation could participate in colitis, the aim of this study was to investigate the role of the NPY Y1 receptor in acute colitis using mice genetically deficient of NPY Y1 receptor. In addition, the Y1 receptor antagonist H409/22, was also investigated. Animals received 5% dextran sulfate sodium (DSS) in drinking water for 7 days. One group of animals also received the Y1 receptor antagonist, administered intraperitoneally twice daily. Disease activity was assessed daily for 7 days in all groups. DSS induced colitis in all animals resulting in weight loss, diarrhea, epithelial damage, crypt shortening, and inflammatory infiltration. However, clinical manifestation of the disease was markedly attenuated in Y1 null mutant mice as well as in mice receiving the Y1 antagonist. Histological analysis showed that tissue damage and ulceration were less severe in Y1-deficient animals. Consistent with the clinical and histological data, capsaicin-induced plasma extravasation was significantly reduced in the gut of Y1 null mutant animals compared with treated wild-type animals. These data indicate that NPY and Y1 receptor are involved in intestinal inflammation and suggest that inhibition of NPY Y1 receptor signaling may provide a novel therapeutic approach in the treatment of colonic inflammation. neurogenic inflammation; dextran sulfate sodium; in vivo animal models ULCERATIVE COLITIS AND CROHN'S disease constitute the two main forms of inflammatory bowel disease (IBD). This disease is characterized by a dysregulated immune response and chronic relapsing inflammation of the gastrointestinal (GI) tract, leading to diarrhea, hemoccult, abdominal pain, weight loss, and anemia.Despite intense research, the etiology of IBDs remains largely unknown. The development of IBD involves interactions among genetic, immunological, and environmental components (46). Other mediators implicated in the pathogenesis of colitis are neuropeptides released from enteric and sensory afferent neurons (37). These peptides have been shown to modulate different aspects of mucosal function, including blood flow and secretion, and may play a role in the recruitment of granulocytes and lymphocytes and in the modulation of mast cell activation (14,18).Stimulation and activation of capsaicin-sensitive sensory nerve endings produce an inflammatory response characterized by vasodilation and plasma extravasation (13). The inflammatory response is mediated by local release of sensory neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) (25). The inflammatory response, termed neurogenic inflammation, is well described in many peripheral organs including the skin, ai...

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Section: And Y1supporting

confidence: 91%

Attenuation of acute experimental colitis by preventing NPY Y1 receptor signaling

Hassani

Lucas

Rozell

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Amplification of cDNA by PCR was performed using the HotStartTaq Master Mix Kit (Qiagen). The primers used were: NPY (NM_012614), 5Ј-GGCCAGATACTACTCCGCTCTGCG-3Ј (forward) and 5Ј-TTCACAGGATGAGATGAGATGTG-3Ј (reverse) (Chottova Dvorakova et al, 2008); PYY (NM_001034080), 5Ј-CTCTGTTCTCCAAACTGCTC-3Ј (forward) and 5Ј-ACCAAACATGCAAGTGAAGTC-3Ј (reverse); PP (NM_012626), 5Ј-CATACTACTGCCTCTCCCTG-3Ј (forward) and 5Ј-GTTTCGTATTGAGCCCTCTG-3Ј (reverse); NPY Y1 receptor (X95507), 5Ј-AAATGTATCACTTGCGGCGTTCA-3Ј (forward) and 5Ј-GCGACCACGATGGAGAGCAG-3Ј (reverse) (Jackerott and Larsson, 1997), Y2 receptor (NM_023968), 5Ј-CCCGGATCTGGAGTAAGCTAAA-3Ј (forward) and 5Ј-GTGGAGCACATCGCAATAATGT-3Ј (reverse) (Chottova Dvorakova et al, 2008); Y4 receptor (NM_031581), 5Ј-TTGCAGTTCTCTGGCTGCCCCTG-3Ј (forward) and 5Ј-CTTGCTACCCATCCTCATAGAT-3Ј (reverse); Y5 receptor (NM_012869), 5Ј-CCAGGCAAAAACCCCCAGCAC-3Ј (forward) and 5Ј-GGCAGTGGATAAGGGCTCTCA-3Ј (reverse); and -actin (NM_031144), 5Ј-TCATCACTATCGGCAATGAGC-3Ј (forward) and 5Ј-CTCCTTCTGCATCCTGTCAGC-3Ј (reverse).…”

Section: Rt-pcrmentioning

confidence: 99%

Neuropeptide Y functions as a facilitator of GDNF-induced budding of the Wolffian duct

et al. 2009

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Ureteric bud (UB) emergence from the Wolffian duct (WD), the initiating step in metanephric kidney morphogenesis, is dependent on GDNF; however, GDNF by itself is generally insufficient to induce robust budding of the isolated WD in culture. Thus, additional factors, presumably peptides or polypeptide growth factors, might be involved. Microarray data from in vivo budding and nonbudding conditions were analyzed using non-negative matrix factorization followed by gene ontology filtering and network analysis to identify sets of genes that are highly regulated during budding. These included the GDNF co-receptors GFR1 and RET, as well as neuropeptide Y (NPY). By using ANOVA with pattern matching, NPY was also found to correlate most significantly to the budded condition with a high degree of connectedness to genes with developmental roles. Exogenous NPY [as well as its homolog, peptide YY (PYY)] augmented GDNF-dependent budding in the isolated WD culture; conversely, inhibition of NPY signaling or perturbation of NPY expression inhibited budding, confirming that NPY facilitates this process. NPY was also found to reverse the decreased budding, the downregulation of RET expression, the mislocalization of GFR1, and the inhibition of AKT phosphorylation that resulted from the addition of BMP4 to the isolated WD cultures, suggesting that NPY acts through the budding pathway and is reciprocally regulated by GDNF and BMP4. Thus, the outgrowth of the UB from the WD might result from a combination of the upregulation of the GDNF receptors together with genes that support GDNF signaling in a feed-forward loop and/or counteraction of the inhibitory pathway regulated by BMP4.

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“…PYYsensitive Y 1 receptors are expressed by neurons of the rat myenteric and submucous plexuses (27). 5-HT synthesizing and releasing neurons are found in the myenteric plexus of guinea pigs (16,22) with neighboring neurons expressing 5-HT 3 receptors (20,57,58).…”

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confidence: 99%

Slowing intestinal transit by PYY depends on serotonergic and opioid pathways

Lin

Neevel

Chen

2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Slowing intestinal transit by PYY depends on serotonergic and opioid pathways. Am J Physiol Gastrointest Liver Physiol 286: G558-G563, 2004; 10.1152/ ajpgi.00278.2003.-Slowing of intestinal transit by fat is abolished by immunoneutralization of peptide YY (PYY), demonstrating a key role for this gut peptide. How PYY slows intestinal transit is not known. We tested the hypothesis that the slowing of intestinal transit by PYY may depend on an ondansetron-sensitive serotonergic pathway and a naloxone-sensitive opioid pathway. In a fistulated dog model, occluding Foley catheters were used to compartmentalize the small intestine into proximal (between fistulas) and distal (beyond midgut fistula) half of gut. Buffer (pH 7.0) was perfused into both proximal and distal gut, and PYY was delivered intravenously. Ondansetron or naloxone was mixed with buffer and delivered into either the proximal or distal half of gut. Intestinal transit was measured across the proximal half of the gut. The slowing of intestinal transit by PYY was abolished when either ondansetron or naloxone was delivered into the proximal, but not the distal gut, to localize the two pathways to the efferent limb of the slowing response. In addition, 5-HT slows intestinal transit with marker recovery decreased from 76.2 Ϯ 3.6% (control) to 33.5 Ϯ 2.4% (5-HT) (P Ͻ 0.0001) but was reversed by naloxone delivered into the proximal gut with marker recovery increased to 79.9 Ϯ 7.2% (P Ͻ 0.0005). We conclude that the slowing of intestinal transit by PYY depends on serotonergic neurotransmission via an opioid pathway. ileal brake; intestinal motility; 5-HT; enteric nervous system PEPTIDE YY (PYY), a distal gut peptide released in response to a fatty meal, slows intestinal transit when administered intravenously (47). In addition to this slowing effect on intestinal transit, PYY is considered an inhibitory peptide, because it suppresses gastrin-stimulated acid secretion (1, 42), pancreatic exocrine secretion (1, 40), CCK release (41), and gastric emptying (47). These inhibitory effects of exogenous PYY suggest that it may be responsible for the ileal brake (49), a response that suppresses the digestive activities of the upper gastrointestinal tract when nutrients such as fat reach the distal gut. Immunoneutralization studies (38) confirmed that PYY is a key mediator of the slowing of intestinal transit by the fat-induced ileal brake. It is not known, however, how PYY slows intestinal transit.Previously, we created a fistulated dog model that divided the small intestine into proximal and distal segments. We used it to show that placing fat in the distal half of small intestine slowed transit in the proximal half of small intestine. Because the luminal content of the proximal and distal intestinal segments were not in continuity, this observation indicated that the fat-induced ileal brake occurred via a reflex, whereby the distal segment exposed to fat served as the afferent limb of the reflex and the proximal segment in which intestinal transit was measured serv...

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Immunocytochemical Localization of the NPY/PYY Y1 Receptor in Enteric Neurons, Endothelial Cells, and Endocrine-like Cells of the Rat Intestinal Tract

Cited by 50 publications

References 52 publications

Attenuation of acute experimental colitis by preventing NPY Y1 receptor signaling

Attenuation of acute experimental colitis by preventing NPY Y1 receptor signaling

Neuropeptide Y functions as a facilitator of GDNF-induced budding of the Wolffian duct

Slowing intestinal transit by PYY depends on serotonergic and opioid pathways

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