Pancreatic Peptide YY mRNA Levels Increase during Adaptation after Small Intestinal Resection

Liu, Carson D.; Hines, Oscar J.; Whang, Edward E.; Laird, Elizabeth C.; Skotzko, Michael J.; Zinner, Michael J.; Ashley, Stanley W.; McFadden, David W.

doi:10.1006/jsre.1995.1002

Cited by 13 publications

(34 citation statements)

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“…Novel Peptide Y2-R agonist and nonpeptide antagonist. (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36) neuroendocrine system on cell growth appear to differ according to each clone: in LNCaP cells, no apparent involvement of the mitogen-activated protein kinase (MAPK)/ extracellular regulated kinase (ERK)1/2 is present, whereas in both androgen-independent clones, DU145 and PC3, NPY treatment rapidly stimulates ERK1/2 phosphorylation, which quickly returns to low basal levels in PC3 cells, but shows a persistent elevation (at least up to 6 hours) in DU145 cells. This different pattern of MAPK/ERK1/2 activation is associated with the opposite effect observed on cell proliferation exerted by the NPY/Y1-R system.…”

Section: Npy System and Prostate Cancermentioning

confidence: 98%

“…Studies on human pancreatic cancer cells (MiaPaCa-2 and BxPC-3) showed that pretreatment with PYY or BIM-43004-1 (a PYY synthetic analog, corresponding to amino acids 22-36) further decreased the cell growth produced by treatment with 5-fluorouracil or leucovorin [39]. Research from cross-linking studies reveal a PYY binding site on the cell membrane of human pancreatic ductal adenocarcinoma cells (MiaPaCa-2 and PANC-1), that could be instrumental in delivering avidin-dye complexes to cancer through tested biotinylated PYY analogs, with lengths ranging from PYY(1-36), PYY(9-36), PYY(14-36), PYY (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36), and PYY (27)(28)(29)(30)(31)(32)(33)(34)(35)(36). PYY showed the highest potency on pancreatic cancer cell growth and provided the optimal binding for the delivery of fluorescent dyes for imaging and therapy [102].…”

Section: Future Perspectivesmentioning

confidence: 99%

“…Moreover, PYY was found to significantly reduce the growth of human pancreatic ductal adenocarcinoma, both in vitro and in vivo models [25,26], and of human breast infiltrative ductal carcinoma [27]. PYY, first isolated in 1983 from porcine intestine [28], is a 36-aminoacid gut hormone predominantly secreted by the enterochromaffin cells of ileum, colon, and rectum in response to meal [29].…”

Section: Introductionmentioning

confidence: 99%

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Relevance of the Neuropeptide Y System in the Biology of Cancer Progression

Ruscica¹,

Dozio²,

Motta³

et al. 2007

CTMC

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The peptides pancreatic polypeptide (PP), peptide YY (PYY), and neuropeptide Y (NPY) share a similar structure, known as PP-fold. Within this family of peptides, NPY, a highly conserved 36-aminoacid residue peptide, is involved in the regulation of a wide range of physiological functions, such as food intake and energy metabolism, as well as in the promotion of some remarkable aspects of tumor progression, including cell proliferation, matrix invasion, metastatization, and angiogenesis. NPY exerts its biological effects through five G-protein coupled receptors, named Y1-, Y2-, Y4-, Y5-, and y6-R, which appear associated with different aspects of oncogenesis. Y1-R seems involved in the modulation of cancer cell proliferation, whereas Y2-R activation appears to promote angiogenesis. The development of NPY receptor subtype selective analogs has helped to elucidate the physiological and pathophysiological role and localization of each receptor and may contribute to a better understanding of the receptor-ligand interaction. The NPY system appears to be variously associated with specific tumors, including neural crest-derived tumors, breast and prostate cancers. In addition to NPY, PYY is also able to affect cancer cell growth in a dose-dependent manner and through Y-Rs. In conclusion, peptides of the NPY family and the related receptors play an important role in the progression of different cancer types, with some molecular specificity according to each step of this process. On this basis, future studies may be directed to the implementation of novel diagnostic and therapeutic approaches targeting this system.

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Section: Npy System and Prostate Cancermentioning

confidence: 98%

Section: Future Perspectivesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Relevance of the Neuropeptide Y System in the Biology of Cancer Progression

Ruscica¹,

Dozio²,

Motta³

et al. 2007

CTMC

View full text Add to dashboard Cite

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“…Moreover, no effective therapy exists at present for treating malabsorption. McFadden et al reported that mRNA and plasma levels of PYY are elevated in certain malabsorptive disorders [75]. These observations, and the findings that PYY inhibits intestinal secretion and promotes absorption and growth through specific receptors, suggest that it is possible to dissociate various effects of PYY and develop Y 2 receptor selective compounds for treating malabsorptive disorders.…”

Section: Malabsorptionmentioning

confidence: 95%

NPY Family of Hormones: Clinical Relevance and Potential Use in Gastrointestinal Disease

Vona-Davis

McFadden²

2007

CTMC

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The neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) family of hormones exhibit a wide variety of biological actions on the mammalian gastrointestinal tract through known G-protein coupled receptor pathways. At least four receptor subtypes, denoted as Y(1), Y(2), Y(4) an Y(5), each with specific affinities to NPY ligands, serve as regulators of mucosal function, gastrointestinal motility and secretion. Investigations to date, however, have implicated the NPY peptides as mediators in the pathogenesis of numerous gastrointestinal disorders, including malabsorption, short gut, inflammatory bowel diseases, and forms of pancreatitis. Our understanding of these diseases and the interactions of NPY peptides have been advanced by the development of receptor agonists and antagonists that can be used experimentally in animal models. Potent selective PYY agonists have been developed that exhibit clinical potential as proabsorptive agents. NPY receptor agonists and antagonists as well as mice harboring null mutations in the Y(1) and Y(4) receptors have provided novel approaches in preventing intestinal inflammation and diarrhea. The use of competitive antagonists and Y(2) receptor knockouts have also aided in understanding secretory tone and electrogenic ion transport in the colon. In the pancreas, PYY suppresses amylase and cytokine release, which would be desirable in the clinical therapy of pancreatitis. Protein/DNA array analysis has revealed that PYY reduces transcription factor binding activity and disrupts signal transduction pathways activated by TNF-alpha in acinar cells. The present review gives an overview of NPY research in gastrointestinal disease and discusses its clinical relevance and potential use as therapy.

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“…These effects include inhibition of gastric acid and exocrine pancreatic secretions, delaying of gastric emptying, slowing of intestinal transit, − enhancement of basal and postprandial absorption, − and inhibition of basal and secretagogue-induced intestinal secretions. − The PYY homologue, neuropeptide Y (NPY), mimics these activities in the intestine but is 5−10-fold less potent than PYY. ,, In addition, PYY, but not NPY, promotes intestinal growth in normal rats 21 as well as those maintained on parenteral nutrition . Moreover, plasma PYY levels and its mucosal mRNA levels are elevated in certain malabsorptive disorders. , These findings suggest that PYY may play a significant role in the physiological regulation of the mammalian gastrointestinal tract.…”

Section: Introductionmentioning

confidence: 99%

Structure−Activity Studies Including a Ψ(CH₂-NH) Scan of Peptide YY (PYY) Active Site, PYY(22−36), for Interaction with Rat Intestinal PYY Receptors: Development of Analogues with Potent in Vivo Activity in the Intestine

et al. 2000

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Peptide YY (PYY) is a gut hormone that inhibits secretion and promotes absorption and growth in the intestinal epithelium. We have performed structure-activity studies with the active site, N-alpha-Ac-PYY(22-36)-NH(2), for interaction with intestinal PYY receptors. Investigation of aromatic substitutions at position 27 resulted in analogues that exhibited potent in vitro antisecretory potencies with N-alpha-Ac-[Trp(27)]PYY(22-36)-NH(2) exhibiting even greater potency than intact PYY. In vivo studies in dogs revealed that this analogue also promoted intestinal absorption of water and electrolytes during continuous intravenous and intraluminal infusion. Investigations carried out to identify features that would enhance stability revealed that incorporation of Trp(30) increased affinity for PYY receptors. A "CH(2)-NH" scan revealed that incorporation of reduced bonds at position 28-29 or 35-36 imparted greater receptor affinity. In general, disubstituted analogues designed based on the results of single substitutions exhibited good receptor affinity with N-alpha-Ac-[Trp(27),CH(2)-NH(35-36)]PYY(22-36)-NH(2) having the greatest affinity (IC(50) = 0.28 nM). Conservative multiple substitutions with Nle-->Leu and Nva-->Val also imparted good affinity. An analogue designed to encompass most of the favored substitutions, N-alpha-Ac-[Nle(24,28),Trp(30),Nva(31), CH(2)-NH(35-36)]PYY(22-36)-NH(2), exhibited a proabsorptive effect in dogs comparable to, but longer lasting than, that of intact hormone. Selected analogues also exhibited good antisecretory potencies in rats with N-alpha-Ac-[Trp(30)]PYY(22-36)-NH(2) being even more potent than PYY. However, the potencies did not correlate well with the PYY receptor affinity or the proabsorptive potencies in dogs. These differences could be due to species effects and/or the involvement of multiple receptors and neuronal elements in controlling the in vivo activity of PYY compounds. PYY(22-36) analogues exhibited good affinity for neuronal Y2 receptors but poor affinity for Y1 receptors. Also, crucial analogues in this series hardly bound to Y4 and Y5 receptors. In summary, we have developed PYY(22-36) analogues which, via interacting with intestinal PYY receptors, promoted potent and long-lasting proabsorptive and antisecretory effects in in vivo models. These compounds or analogues based on them may have useful clinical application in treating malabsorptive disorders observed under a variety of conditions.

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Pancreatic Peptide YY mRNA Levels Increase during Adaptation after Small Intestinal Resection

Cited by 13 publications

References 0 publications

Relevance of the Neuropeptide Y System in the Biology of Cancer Progression

Relevance of the Neuropeptide Y System in the Biology of Cancer Progression

NPY Family of Hormones: Clinical Relevance and Potential Use in Gastrointestinal Disease

Structure−Activity Studies Including a Ψ(CH₂-NH) Scan of Peptide YY (PYY) Active Site, PYY(22−36), for Interaction with Rat Intestinal PYY Receptors: Development of Analogues with Potent in Vivo Activity in the Intestine

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Pancreatic Peptide YY mRNA Levels Increase during Adaptation after Small Intestinal Resection

Cited by 13 publications

References 0 publications

Relevance of the Neuropeptide Y System in the Biology of Cancer Progression

Relevance of the Neuropeptide Y System in the Biology of Cancer Progression

NPY Family of Hormones: Clinical Relevance and Potential Use in Gastrointestinal Disease

Structure−Activity Studies Including a Ψ(CH2-NH) Scan of Peptide YY (PYY) Active Site, PYY(22−36), for Interaction with Rat Intestinal PYY Receptors: Development of Analogues with Potent in Vivo Activity in the Intestine

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Structure−Activity Studies Including a Ψ(CH₂-NH) Scan of Peptide YY (PYY) Active Site, PYY(22−36), for Interaction with Rat Intestinal PYY Receptors: Development of Analogues with Potent in Vivo Activity in the Intestine