Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Peptide YY”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1997

Characterization of Y3 receptor-mediated synaptic inhibition by chimeric neuropeptide Y-peptide YY peptides in the rat brainstem.

1. Neuropeptide Y (NPY) and peptide YY (PYY) act at receptors referred to as Y1 and Y2, while the Y3 receptor is specific to NPY and does not recognize PYY. The effects of NPY, its related peptides and a series of newly constructed chimeric NPY-PYY peptides were examined on excitatory and inhibitory postsynaptic currents (e.p.s.cs and i.p.s.cs, respectively) in rat dorsomedial nucleus tractus solitarius (NTS) neurones recorded in coronal brainstem slices. Monosynaptic activity was evoked by electrical stimulation in the region of the tractus solitarius. 2. NPY (5-500 nM) inhibited e.p.s.cs and i.p.s.cs in a concentration-dependent manner. In contrast, PYY (500 nM) failed to affect either e.p.s.cs or i.p.s.cs. The N- and C-terminal parts of a series of chimeric NPY-PYY peptides were joined at positions where NPY and PYY sequences differ. In binding experiments the chimeric peptides were all about equipotent with NPY and PYY in displacing [125I]-PYY from Y1 and Y2 binding sites on SK-N-MC cells and rat hippocampus respectively. 3. In the whole cell voltage clamp recordings of NTS neurones, NPY(1-23)-PYY(24-36) and NPY(1-14)-PYY(15-36) evoked a concentration-dependent inhibition of e.p.s.cs and i.p.s.cs, while NPY(1-7)-PYY(8-36) and NPY(1-3)-PYY(4-36) were inactive. The only differences in amino acid residues between NPY(1-14)-PYY(15-36) and NPY(1-7)-PYY(8-36) reside in positions 13 and 14. 4. Furthermore, [Pro34]NPY (500 nM) was equivalent in potency to NPY itself at inhibiting monosynaptic transmission in NTS, while [Leu31,Pro34]NPY and pancreatic polypeptide (both at 500 nM) failed to affect synaptic transmission. 5. The present study has shown that NPY acts at Y3 receptors to suppress both excitatory and inhibitory currents in the NTS. The different efficacy of the chimeric NPY-PYY peptides suggests that positions 13 and 14 are of great importance for Y3 receptor recognition. Finally, this receptor type readily recognizes [Pro34]NPY, but not [Leu31,Pro34]NPY.

Amino Acid Sequence↗
PubMed1987

Distribution and postprandial release of porcine peptide YY.

Peptide YY (PYY), a thirty-six amino acid intestinal hormonal peptide with a tyrosine residue at each end (hence YY as Y represents tyrosine in the new peptide nomenclature), was found throughout the gastrointestinal tract of the pig. Concentrations were very low in the foregut (antrum, 3.4 +/- 0.3 pmol/g; duodenum, 1.1 +/- 1.5 pmol/g), higher in the distal small intestine (ileum, 100 +/- 13 pmol/g) and very high in the large bowel (descending colon, 270 +/- 45 pmol/g). Peptide YY was found to circulate in plasma and concentrations rose substantially in response to eating (fasting, 138 +/- 15 pmol/l; postprandial, 263 +/- 21 pmol/l; P less than 0.001). There was a small but significant portal/arterial gradient in postprandial PYY levels. More than 90% of the immunoreactive PYY in gut extracts eluted, on gel permeation chromatography, in an identical position to pure PYY standard, but small amounts of higher molecular weight material, possibly precursors, were detected. In contrast, plasma from fasting pigs contained a large proportion (60-70%) of these large molecular forms. These findings suggest that the putative pro-PYY may be cleared more slowly from the circulation than the 36 amino acid hormonal peptide. The high concentrations of immunoreactive PYY in the circulation of the young pig may reflect a species difference between pig and man or may indicate an important role for PYY in the developing animal.

Animals↗
PubMed2002

Central and peripheral regulation of gastric acid secretion by peptide YY.

Peptide YY (PYY) released postprandially from the ileum and colon displays a potent inhibition of cephalic and gastric phases of gastric acid secretion through both central and peripheral mechanisms. To modulate vagal regulation of gastric functions, circulating PYY enters the brain through the area postrema and the nucleus of the solitary tract, where it exerts a stimulatory action through PYY-preferring Y1-like receptors, and an inhibitory action through Y2 receptors. In the gastric mucosa, PYY binds to Y1 receptors in the enterochromaffin-like cells to inhibit gastrin-stimulated histamine release and calcium signaling via a pertussis toxin-sensitive pathway.

Animals↗
PubMed1983

Immunocytochemical evidence for a substance related to the bovine pancreatic polypeptide-peptide YY group of peptides in the human fetal gastrointestinal tract.

The time of the first appearance and distribution of substance(s) reacting with the bovine pancreatic polypeptide (BPP) antiserum No. 146-6, i.e., BPP-like immunoreactivity, were studied in the gastrointestinal tract of 5-24-week-old human fetuses using an indirect immunoperoxidase method. The first immunostaining was identified at the 12th week of gestation in the oxyntic and colonic mucosa, and at the 10th week in the ileum. Serial sections alternately labelled with BPP and glicentin (GLI-1) antisera show several patterns. In the enteric and oxyntic mucosa, there is a cell population reacting only with the GLI-1 antiserum intermixed with cells containing both BPP-like and GLI-1-like immunoreactivities. In the oxyntic mucosa, however, certain cells might store BPP-like material only. Specificity tests illustrate cross-reactivity occurring in immunocytochemical studies of extrapancreatic BPP. The ability of synthetic BPP or a chemically related peptide, peptide YY to abolish the BPP antiserum immunoreaction, as well as previous radioimmunoassay data, raise the question of the presence of authentic BPP in GLI-1-containing cells.

Animals↗
PubMed1995

Characterization of neuropeptide Y binding sites in rat brain membrane preparations using [125I][Leu31,Pro34]peptide YY and [125I]peptide YY3-36 as selective Y1 and Y2 radioligands.

The peptide YY (PYY)-derivatives [Leu31,Pro34]PYY and PYY3-36 were respectively developed as selective Y1 and Y2 radioligands devoid of affinity for the Y3 receptor subtype. Each analog was iodinated by the chloramine T method after a purification by reverse-phase high-performance liquid chromatography. Both radioligands bind with high affinity, low capacity and in a time-dependent and saturable manner to specific sites present in rat frontoparietal cortical or hippocampal membrane preparations. [125I][Leu31,Pro34]PYY demonstrated apparent affinities (Kd) of 0.42 +/- 0.07 and 0.22 +/- 0.08 nM and maximal capacities (Bmax) of 185 +/- 14 and 33 +/- 4 fmol/mg of protein to a single class of sites in cortical and hippocampal membrane homogenates, respectively. Conversely, [125I]PYY3-36 apparently bound to a greater amount of sites in hippocampal (Bmax of 109 +/- 13 fmol/mg of protein; Kd of 0.13 +/- 0.03 mM) compared with cortical (Bmax of 33 +/- 5 fmol/mg of protein; Kd of 0.37 +/- 0.06 nM) membrane preparations, which suggests the differential enrichment of these two brain regions with a given neuropeptide Y (NPY) receptor subtype. The comparative ligand selectivity profile of these two radiolabeled PYY derivatives confirmed this hypothesis and revealed that, although the rat frontoparietal cortex is enriched with Y1 sites, Y2, receptor binding sites are most abundant in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

[Antisecretory effects of YY peptide and neuropeptide Y at three levels of the small intestine in rats].

OBJECTIVES AND METHODS: The purpose of this study was to compare the effects of peptide YY (PYY) and neuropeptide Y (NPY) on VIP- and PGE2-stimulated intestinal net water flux at three different levels of the small intestine (duodenum, jejunum, ileum), by a technique of in situ closed loops in anaesthetised rats. RESULTS: VIP-stimulated net water flux was efficiently inhibited by both peptides at all three intestinal levels studied; PYY (ID50 about 30 pmol/kg.h) was 3 to 18 fold more potent than NPY. PGE2-stimulated net water flux was also efficiently inhibited in the jejunum and ileum; PYY (ID50 about 10 pmol/kg.h) was 30 to 90 fold more potent than NPY. A 30% inhibition of PGE2-stimulated net water flux could only be achieved in the duodenum with the largest dose of either peptide used in this study. CONCLUSIONS: PYY and NPY display potent inhibitory effects of stimulated net water flux at the three studied levels of the small intestine, except in the PGE2-stimulated duodenum. The PYY ID50s measured suggest that PYY may have a physiological action in regulating small intestinal water flux in the rat.

Animals↗
PubMed1989

Peptide-YY and neuropeptide-Y inhibit vasoactive intestinal peptide-stimulated adenosine 3',5'-monophosphate production in rat small intestine: structural requirements of peptides for interacting with peptide-YY-preferring receptors.

Previous binding studies indicated that peptide-YY (PYY) and neuropeptide-Y (NPY) shared a common PYY-preferring receptor site in rat small intestinal epithelium. We showed here that PYY and NPY inhibited vasoactive intestinal peptide (VIP)-stimulated cAMP production in epithelial cells isolated from rat small intestine and examined their structure-activity relationship. Inhibition of VIP-stimulated cAMP by PYY or NPY is time and dose dependent; half-maximal effects were observed for 10 and 107 nM, respectively. In contrast, the structurally related peptide, pancreatic polypeptide, was only active at 1 microM. PYY or NPY reduced the efficacy of VIP by about 50% without altering its potency. Both peptides also suppressed prostaglandin E1-, prostaglandin E2-, and forskolin-stimulated cAMP production and reduced basal cAMP levels. Their inhibitory effects were observed throughout the small intestine, including duodenum, jejunum, and ileum, but not in large intestine. PYY or NPY and epinephrine (through alpha 2-adrenergic receptors) did not exert additive inhibitory effects on intestinal cAMP production. Several fragments of PYY and NPY were used to characterize their structural requirement for inhibiting VIP-stimulated cAMP production and competing with [125I]PYY for binding to intestinal membranes. A highly significant correlation was observed between IC50 values measured in the two assays. No partial sequence of PYY retained the full activity of intact PYY, but the C-terminal portion of PYY was shown to be much more important than the N-terminal portion. Deletion of 21 amino acids from the N-terminus [PYY-(22-36)] only resulted in a 4- to 5-fold decrease in potency compared to that of PYY-(1-36). In contrast, PYY-(27-36) exhibited a drastic loss of potency. The N-terminal fragments PYY-(1-22) and PYY-(1-28) also had very low potencies. Similar results were obtained with NPY fragments. These results provide the first insight on the negative coupling of PYY-preferring receptors with the cAMP production system in small intestine and evidence of the crucial role of the C-terminal portion of PYY in interaction with these receptors.

Amino Acid Sequence↗
PubMedDate not supplied

Syntheses and receptor affinities of partial sequences of peptide YY (PYY).

Peptide YY (PYY) is a 36 residue peptide amide isolated from porcine intestine. It has distinct structural homology with neuropeptide Y (NPY) and pancreatic polypeptide (PP). Endocrine cells of pancreas and gut of mammals have been shown to contain PYY-like immunoreactivity. PYY exhibits both NPY- and PP-like biological activities such as inhibition of exocrine pancreatic secretion, stimulation of feeding, vasoconstriction and inhibition of intestinal motility. PYY has also been shown to be a potent inhibitor of intestinal fluid and electrolyte secretion. Although PYY-preferring receptors have been identified and characterized in rat jejunal epithelium, no structure-activity studies with PYY and receptors have been reported. We therefore synthesized a number of partial sequences of PYY and evaluated their binding relative to the intact hormone in a radioreceptor assay. This investigation has resulted in identifying the receptor binding region of PYY. This information may prove useful in designing agonistic and antagonistic peptides not only for PYY but also for other structurally related hormones such as NPY.

Amino Acid Sequence↗
PubMed1994

[Pro34]peptide YY is a Y1-selective agonist at peptide YY/neuropeptide Y receptors.

We have investigated binding and functional effects of a new peptide YY analogue, [Pro34]peptide YY, at Y1 and Y2-like subtypes of receptors for peptide YY and neuropeptide Y. In binding studies [Pro34]peptide YY had a similarly high affinity as peptide YY to human Y1-like receptors in SK-N-MC cells, a human neuroblastoma cell line of presumed neurogenic origin, and HEL cells, a human cell line derived from a patient with Hodgkin's disease. In functional studies [Pro34]peptide YY stimulated Ca2+ elevations in both Y1-like receptor cell lines with similar potency and efficacy as peptide YY. In contrast to peptide YY [Pro34]peptide YY was 1000-fold less potent in binding to Y2-like receptors in porcine splenic membranes and lacked agonistic effects in another Y2-like receptor-mediated model system, i.e. inhibition of [3H]serotonin release from rat cerebral cortical slices. Thus, [Pro34]peptide YY is a highly Y1-selective full agonist of peptide YY/neuropeptide Y receptors. [Pro34]peptide YY could be useful for studying the importance of Y receptor subtypes in mediating peptide YY physiological actions.

Amino Acid Sequence↗
PubMed1987

The amino-acid sequences of sculpin islet somatostatin-28 and peptide YY.

Two pancreatic peptides, somatostatin-28 and peptide YY, have been isolated from the Brockmann bodies of the teleost fish Cottus scorpius (daddy sculpin). Following purification by reverse-phase HPLC, each peptide was sequenced completely through to the carboxyl-terminus by gas-phase Edman degradation. Somatostatin-28 was the major form of somatostatin detected and is similar to the gene II product from anglerfish. Peptide YY (36 amino acids) more closely resembles porcine neuropeptide YY and intestinal peptide YY than it does the pancreatic polypeptides.

Amino Acid Sequence↗
PubMed1998

Peptide YY, glucagon-like peptide-1, and neurotensin responses to luminal factors in the isolated vascularly perfused rat ileum.

Exposure of the ileum to nutrients markedly inhibits several upper gastrointestinal functions. Hormonal peptides of the ileal wall, i.e. peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and neurotensin (NT), are thought to play a role in this negative feedback mechanism. The present study was conducted to comparatively assess the secretion of PYY, GLP-1, and NT upon luminal infusion of a variety of individual luminal factors in the isolated vascularly perfused rat ileum preparation. PYY, GLP-1, and NT were measured in the portal effluent with specific RIAs. Glucose (250 mM) induced a pronounced release of the three peptides, whereas a physiological concentration of 5 mM did not induce peptide secretion. Peptone (5%, wt/vol) evoked a sustained release of PYY, GLP-1, and NT. Only NT secretion was increased upon luminal administration of 100 mM sodium oleate. Short chain fatty acids (20 mM) evoked an early and transient release of the three peptides. In contrast, taurocholate (20 mM) induced a sustained release of PYY, GLP-1, and NT, but the threshold concentration for peptide release was lower for NT than for PYY or GLP-1. Cellulose or pectin (0.5%, wt/vol) did not modify peptide secretion. In conclusion, glucose and peptone are potent stimulants of PYY, GLP-1, and NT release. Only NT is released upon oleic acid stimulation. Finally, taurocholate is a potent stimulant of the release of the three peptides. Overall, PYY, GLP-1, and NT may participate cooperatively in the ileal brake. As relatively high concentrations of the various stimulants were required to elicit peptide release, it seems likely that this mechanism operates in cases of maldigestion or malabsorption.

Animal Nutritional Physiological Phenomena↗
PubMed1999

Autoradiographic reevaluation of the binding properties of 125I-[Leu31,Pro34]peptide YY and 125I-peptide YY3-36 to neuropeptide Y receptor subtypes in rat forebrain.

125I-[Leu31,Pro34]peptide YY (PYY) and 125I-PYY3-36, initially described as selective neuropeptide Y Y1 and Y2 receptor ligands, respectively, were recently shown to label also Y4 and Y5 receptors. We used receptor autoradiography to assess whether these ligands can be reliably used to investigate the various neuropeptide Y receptors in rat forebrain. In most of the brain regions examined (in coronal sections at the level of dorsal hippocampus), specific 125I-[Leu31,Pro34]PYY binding was completely inhibited by 1 microM BIBP-3226, a selective Y1 receptor ligand, but unaffected by 10 nM rat pancreatic polypeptide, selectively inhibiting Y4 receptors, suggesting that Y4 receptors are present in negligible numbers compared with Y1 receptors in the areas examined. Significant numbers of BIBP-3226-insensitive 125I-[Leu31,Pro34]PYY binding sites were measured in the CA3 subfield of the hippocampus only, possibly representing Y5 receptors. 125I-PYY3-36 binding was unchanged by 1 microM BIBP-3226, whereas a population of 125I-PYY3-36 binding sites was sensitive to 100 nM [Leu31,Pro34]neuropeptide Y, likely representing Y5 receptors. The possibility of distinguishing between Y2 and Y5 receptors using 125I-PYY3-36 as radioligand was validated by their different regional distribution and their distinct changes 24 h after kainate seizures, i.e., binding to Y5 receptors was selectively decreased in the outer cortex, whereas binding to Y2 receptors was enhanced in the hippocampus. Thus, the use of selective unlabeled compounds is required for distinguishing the various receptor subtypes labeled by 125I-[Leu31,Pro34]PYY and 125I-PYY3-36 in rat brain tissue.

Animals↗
PubMed1994

Mechanisms underlying the insulinostatic effect of peptide YY in mouse pancreatic islets.

Peptide YY is an insulinostatic peptide which is released into the circulation from the intestinal mucosa upon food intake. Peptide YY is also co-stored with glucagon in the secretory granules of the pancreatic alpha cells. We examined the mechanisms underlying the insulinostatic effect of peptide YY in isolated mouse pancreatic islets. We found that peptide YY (0.1 nmol/l-1 mumol/l) inhibited glucose (11.1 mmol/l)-stimulated insulin secretion from incubated isolated islets, with a maximal inhibition of approximately 70% observed at a dose of 1 nmol/l (p < 0.001). Also in perifused islets the peptide (1 nmol/l) inhibited insulin secretion in response to 11.1 mmol/l glucose (p < 0.001). Furthermore, peptide YY inhibited glucose-stimulated cyclic AMP formation (by 67%, p < 0.05), and insulin secretion stimulated by dibutyryl cyclic AMP (p < 0.01). In contrast, the peptide was without effect both on the cytoplasmic Ca2+ concentration in dispersed mouse islet-cell suspensions as measured by the FURA 2-AM technique, and on insulin release in isolated islets, when stimulated by the protein kinase C-activator 12-O-tetradecanoyl phorbol 13-acetate. Finally, in pre-labelled perifused islets, peptide YY caused a small and transient increase in the 86Rb+ efflux (p < 0.001), but only in the absence of extracellular Ca2+. We conclude that peptide YY inhibits glucose-stimulated insulin secretion from isolated mouse islets by inhibiting two different steps in the cyclic AMP cascade, that is, both the accumulation and the action of the cyclic nucleotide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Solution synthesis of human peptide YY (hPYY).

Human peptide YY (hPYY) was synthesized in a conventional manner by assembling six peptide fragments followed by deprotection with 1 M trimethylsilyl trifluoromethanesulfonate (TMSOTf)-thioanisole in trifluoroacetic acid (TFA). After purification by gel-filtration on Sephadex G-25, followed by reversed-phase high-performance liquid chromatography, a highly purified sample of synthetic hPYY was obtained. When administered in dogs, synthetic hPYY was as active as synthetic porcine PYY in terms of the effects on systemic arterial blood pressure, and splanchnic blood flow.

Amino Acid Sequence↗
PubMed1999

Comparison of the postprandial release of peptide YY and proglucagon-derived peptides in the rat.

Endocrine L-cells of the distal intestine synthesize both peptide YY (PYY) and proglucagon-derived peptides (PGDPs), whose release has been reported to be either parallel or selective. Here we compare the release mechanisms of PYY, glucagon-like peptide-1 (GLP-1), and oxyntomodulin-like immunoreactivity (OLI) in vivo. Anaesthetized rats were intraduodenally (ID) given either a mixed semi-liquid meal or oleic acid, or they received oleic acid or short chain fatty acids (SCFA) intracolonically (IC). The ID meal released the three peptides with a similar time-course (peak at 30 min); ID oleic acid produced a progressive release of PYY and OLI, while GLP-1 release was less. IC oleic acid or SCFA released smaller (but significant) amounts of PYY but no OLI or GLP-1. Hexamethonium inhibited most of the response to the ID meal and ID oleic acid, but did not change the PYY response to IC oleic acid. NG-nitro-l-arginine methyl ester (l-NAME, a nitric oxide synthase inhibitor) inhibited meal-induced PYY release and left OLI and GLP-1 unaffected. BW10 (a gastrin-releasing peptide antagonist) had no effect on the meal-induced release of either peptide. These results suggest a parallel initial release of PYY, OLI and GLP-1 after the ID meal, or oleic acid, by an indirect mechanism triggered in the proximal bowel, using nicotinic synapses, and involving nitric oxide release for PYY and an unknown mediator for PGDPs. For PYY there is a later phase of peptide release, probably induced by direct contact between nutrients and colonic L-cells.

Animals↗
PubMed1988

Adrenergic pathway in the inhibition of pancreatic secretion by peptide YY in dogs.

Peptide YY (PYY) is released by perfusion of an ileocolonic segment with oleate and inhibits exocrine pancreatic secretion. This study was designed to determine the role of the adrenergic pathway in the PYY-induced inhibition of pancreatic secretion. After intravenous administration of PYY, there was a dose-dependent inhibition of pancreatic HCO3 and protein responses to secretin, cholecystokinin, and feeding in conscious dogs and a reduction in pancreatic blood flow in anesthetized animals. These inhibitory effects of PYY on pancreatic secretion and blood flow were abolished in the presence of combined phentolamine and propranolol. Ileal perfusion with oleate caused a rise in plasma PYY levels similar to that observed after intravenous infusion of exogenous PYY. Combined alpha- and beta-adrenergic blockade also antagonized the effects of ileal perfusion with oleate on hormonal and postprandial pancreatic secretion. We conclude that exogenous PYY or endogenous PYY released by ileal oleate inhibits pancreatic secretory responses to exogenous secretin, cholecystokinin, or a meal and causes pancreatic vasoconstriction. Both these effects are mediated, at least in part, by the adrenergic pathway.

Animals↗
PubMed1992

Extrinsic neural contribution to ileal peptide YY (PYY) release.

Peptide YY (PYY) release into the ileal lumen is stimulated by cholecystokinin (CCK) and glucose ingestion. Previous data have implicated vagal activity in the mediation of PYY release into both the systemic circulation and the ileal lumen. The present study was designed to evaluate extrinsic neural involvement in CCK and glucose-stimulated circulating and ileal intraluminal PYY release. Distal ileal Thiry-Vella loops (TVL) of 25 cm were created in seven mongrel dogs. On separate days fasted dogs were given continuous infusions of CCK at 500 ng/kg/hr during the first hour of the study or an oral glucose (1.5 g/kg) tolerance test (OGTT) was performed. Peripheral blood samples and ileal effusates were collected before tests and following either CCK or glucose stimulation for 120 min at 20-min intervals. Ileal PYY recoveries were measured by the instillation and collection of 20 cc of normal saline from the TVL for each 20-min period. The dogs were again tested after surgical denervation of the TVL. OGTT resulted in a significant rise of PYY recovery from the TVL (P less than 0.05), while not affecting circulating PYY. Intravenous CCK resulted in significant increases in both plasma and ileal PYY concentrations (P less than 0.05). Denervation of the TVL decreased PYY recovery from the TVL after both CCK and OGTT, whereas this procedure did not affect circulating PYY levels or basal luminal levels. These data demonstrate the inhibition of CCK- and glucose-stimulated ileal PYY recovery from denervated ileal loops. The extrinsic neural pathways are involved in the mediation of glucose- and CCK-stimulated mechanisms for ileal PYY release.

Animals↗