Localization and characterization of neuropeptide Y binding sites in porcine and human colon

Walsh, David A.; Wharton, John; Blake, David R.; Polak, Julia M.

doi:10.1111/j.1476-5381.1993.tb12800.x

Cited by 23 publications

(18 citation statements)

References 32 publications

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“…This sequence was also identical to that of the Y2 receptor cDNA from rat hypothalamus that was reported during the course of our study (38), and the deduced amino acid sequence was identical to the previously published rat Y2 amino acid sequence (37). These results clearly demonstrate the presence of Y2 receptor transcripts in the epithelial cell population of intestinal cells in addition to the previously reported expression only in the enteric nervous system (34,39).…”

Section: Figsupporting

confidence: 70%

“…Together these observations indicate the activation of multiple Y receptors and/or intracellular signaling systems in the hB-RIE 380i cells. The expression of the Y1 and Y2 receptor subtypes in the intestine has previously been determined (34,35); however, the Y2 receptor had not yet been identified in intestinal epithelial cells. Therefore, we tested for the presence of a number of Y receptors previously identified in various tissues and species.…”

Section: Cd63 Expression In Cells Forming Differentiated Clusters In mentioning

confidence: 99%

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Y Receptor-mediated Induction of CD63 Transcripts, a Tetraspanin Determined To Be Necessary for Differentiation of the Intestinal Epithelial Cell Line, hBRIE 380i Cells

Halldén¹,

Hadi²,

Hong³

et al. 1999

Journal of Biological Chemistry

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Peptide YY (PYY) and neuropeptide Y (NPY) are peptides that coordinate intestinal activities in response to luminal and neuronal signals. In this study, using the rat hybrid small intestinal epithelial cell line, hBRIE 380i cells, we demonstrated that PYY-and NPY-induced rearrangement of actin filaments may be in part through a Y1␣ and/or a nonneuronal Y2 receptor, which were cloned from both the intestinal mucosa and the hBRIE 380i cells. A number of PYY/NPY-responsive genes were also identified by subtractive hybridization of the hBRIE 380i cells in the presence or absence of a 6-h treatment with PYY. Several of these genes coded for proteins associated with the cell cytoskeleton or extracellular matrix. One of these proteins was the transmembrane-4 superfamily protein CD63, previously shown to associate with ␤ 1 -integrin and implicated in cell adhesion. CD63 immunoreactivity, using antibody to the extracellular domain, was highest in the differentiated cell clusters of the hBRIE 380i cells. The hBRIE 380i cells transfected with antisense CD63 cDNA lost these differentiated clusters. These studies suggest a new role for NPY and PYY in modulating differentiation through cytoskeletal associated proteins.Regulatory peptides common to the intestine and nerves (neuro-gut regulatory peptides) are unique chemical mediators released from receptosecretory and/or neurosecretory cells having multiple biological actions. These peptides can act as neurotransmitters, neurocrine, endocrine, or paracrine agents and share a common function in the coordination of intestinal activities in response to luminal signals or signals originating from peripheral tissues. Despite the range of diversity of their biological effects, there is one recurring biological observation that seems to link many of these peptides, their ability to act as factors affecting growth or differentiation of the intestinal mucosa. Differentiation and regulation of growth of complex tissues, such as the intestine, are not only determined by growth factors but also by intracellular signals generated by the interactions between cells and their extracellular matrix (ECM) 1 (1).In intestinal epithelial cells, part of the ECM occurs in the form of a basement membrane that provides these cells with positional information and signals that initiate the organization of intracellular structure and cellular behavior. A factor probably important for the positional cues for differentiation in the intestinal mucosa is the potential link between the ECM of the lamina propria and the process of cellular migration from crypt to villus. Although over the past years there have been studies on the growth effects for specific peptides such as cholecystokinin (2), bombesin (3), vasopressin, gastrin (4, 5), and peptide YY (PYY) (6), to name a few, the contribution of these peptides to intestinal differentiation remains relatively unexplored. Such investigations were limited in the past primarily due to the lack of an appropriate cell culture model that mimicked some of the critica...

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Section: Figsupporting

confidence: 70%

Section: Cd63 Expression In Cells Forming Differentiated Clusters In mentioning

confidence: 99%

Y Receptor-mediated Induction of CD63 Transcripts, a Tetraspanin Determined To Be Necessary for Differentiation of the Intestinal Epithelial Cell Line, hBRIE 380i Cells

Halldén¹,

Hadi²,

Hong³

et al. 1999

Journal of Biological Chemistry

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“…Throughout the rat intestine, specific Y1-R immunoreactivity could be localized to many nerve cell bodies of the submucosal and myenteric plexi. Previous studies have also demonstrated the presence of NPY/PYY binding sites in submucosal and myenteric neurons by receptor autoradiography (Walsh et al 1993;Mao et al 1996). These studies, however, were not able to differentiate between NPY/PYY receptor subtypes.…”

Section: Discussionmentioning

confidence: 83%

“…Earlier studies have localized NPY and PYY binding sites to submucosal and myenteric plexi in the gastrointestinal tract using receptor autoradiography (Walsh et al 1993;Mao et al 1996). The identity of these binding sites was further analyzed using the NPY analogues [Leu 31 , Pro 34 ]-NPY and NPY , which preferentially bind to the Y1-R and the Y2 receptor, respectively.…”

mentioning

confidence: 99%

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

Jackerott

Larsson

1997

J Histochem Cytochem.

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SUMMARY Neuropeptide Y (NPY) and peptide YY (PYY) are structurally related peptides that are considered to mediate inhibitory actions on gastrointestinal motility, secretion, and blood flow. Several receptor subtypes for these peptides have been identified and the Y1, Y2, Y4/PP1, Y5, and Y5/PP2/Y2b receptors have been cloned. In this article we report the immunocytochemical localization of the Y1 receptor to myenteric and submucosal nerve cell bodies, endothelial cells, and scattered endocrine-like cells of rat intestinal tract. Moreover, double immunofluorescence demonstrates that subpopulations of the Y1 receptorpositive nerve cell bodies are immunopositive for NPY, vasoactive intestinal polypeptide, and nitric oxide synthase. In part, such co-localizations were made possible by use of peroxidase-mediated deposition of tyramide, which permitted use of antisera derived from the same species. Our observations suggest the existence of multiple neuronal, endothelial, and endocrine target sites for NPY and PYY and that some of the actions of these regulatory peptides can be mediated by vasoactive intestinal peptide and nitric oxide synthase.

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“…NPY-immunoreactive nerve fibers are abundant in GI tract (22,23). With the use of receptor autoradiography, NPY and peptide YY (PYY) binding sites have been localized to submucosal and myenteric plexi (30,45). In the GI tract, NPY and PYY have been shown to be potent inhibitors of intestinal fluid, electrolyte secretion, and motility (36, 38).…”

mentioning

confidence: 99%

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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Localization and characterization of neuropeptide Y binding sites in porcine and human colon

Cited by 23 publications

References 32 publications

Y Receptor-mediated Induction of CD63 Transcripts, a Tetraspanin Determined To Be Necessary for Differentiation of the Intestinal Epithelial Cell Line, hBRIE 380i Cells

Y Receptor-mediated Induction of CD63 Transcripts, a Tetraspanin Determined To Be Necessary for Differentiation of the Intestinal Epithelial Cell Line, hBRIE 380i Cells

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

Attenuation of acute experimental colitis by preventing NPY Y1 receptor signaling

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