Disease relevance of PPY

• However, the PPY- and PP-positive cells did not relate to the increased EC. and It is therefore suggested that the altered PYY in the colonic mucosa may partially contribute to the etiopathology of colonic inertia [1].
• The inhibitory effect of hPP was abolished when cells were incubated with pertussis toxin, indicating a pertussis toxin-sensitive G(i) protein-mediated event [2].
• The same concentration of antagonist abolished responses to PYY and [Leu31,Pro34]NPY but had no effect upon human pancreatic polypeptide (hPP) in monolayer cultures of the human adenocarcinoma cell line, Colony-6 [3].
• We propose that estimation of the PP content of medullary carcinoma of thyroid may be a useful means of differentiating familial and sporadic types [4].
• Implants of diethylstilbestrol inducing anterior pituitary prolactinomas in female Fischer-344 rats produced a considerable elevation of high-affinity binding of either rat or human pancreatic polypeptide (hPP) [5].

Psychiatry related information on PPY

• Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats [6].
• Previous findings that PP release is diminished in obesity, together with the present findings of PP increase in anorexia nervosa, suggest that this peptide may play a role in appetite control mechanisms [7].
• Increased plasma pancreatic polypeptide in chronic alcohol abuse [8].
• hPP and gastrin response to a liquid meal and oral glucose during prolonged severe exercise, caloric deficit, and sleep deprivation [9].
• Fasting antral, duodenal, and jejunal motor activity and plasma motilin and pancreatic polypeptide were studied in 14 patients with systemic sclerosis, 6 and 9 without clinical evidence of small bowel involvement, and 8 healthy control subjects [10].

High impact information on PPY

• The responses of plasma epinephrine and pancreatic polypeptide and the frequency of symptoms of hypoglycemia were lowest in the group with the lowest glycosylated hemoglobin values [11].
• Immunoperoxidase staining of this patient's liver-biopsy specimen showed that the islets contained insulin, glucagon, and somatostatin but not pancreatic polypeptide [12].
• Thus, although its diagnostic sensitivity is low, pancreatic polypeptide appears to be a useful adjunctive marker of many pancreatic endocrine tumors, and the atropine suppression test can be used to distinguish normal from tumor-related secretion of the polypeptide [13].
• To examine the functional role of peptides found within suprachiasmatic neurons, avian pancreatic polypeptide and vasopressin were microinjected into the suprachiasmatic region [14].
• Avian pancreatic polypeptide phase shifts hamster circadian rhythms when microinjected into the suprachiasmatic region [14].

Chemical compound and disease context of PPY

• The aim of the present study was to investigate whether low circulating PP is associated with weight gain in Pima Indians [15].
• Serum pancreatic polypeptide (PP), gastric inhibitory polypeptide (GIP), insulin and glucose responses to meal stimulation were studied in 10 normal weight patients, 13 normal obese patients and 7 patients with Prader-Willi syndrome (PWS) associated obesity [16].
• Action of omeprazole (a benzimidazole derivative) on secretory responses to sham feeding and pentagastrin and upon serum gastrin and pancreatic polypeptide in duodenal ulcer patients [17].
• The effects of omeprazole, a benzimidazole derivative, have been determined on the secretory responses to modified sham feeding and pentagastrin, and upon serum gastrin and pancreatic polypeptide concentrations in duodenal ulcer patients [17].
• Intravenous administration of 1 mg atropine to all 19 affected members of MEN I families and to 8 normal control subjects inhibited serum PP in all of them [18].

Biological context of PPY

• Examination of cell hybrids with chromosomal rearrangements assigned PPY to the p11.1-qter region and NPY to the pter-q22 region of their respective chromosomes [19].
• Similar gene duplication events of the PYY-PPY gene cluster have also occurred in other species, including cow and baboon, but have not been confirmed in the rat and mouse genomes [20].
• The duplication of the PYY gene that generated the PPY gene appears to have resulted in a relaxation of conservative pressure on the functional domain with the result that the amino acid sequences of tetrapod PYYs are more variable than the PYYs of jawed fish [21].
• Genes encoding pancreatic polypeptide and neuropeptide Y are on human chromosomes 17 and 7 [19].
• After stable transfection of the cDNA into human embryonic kidney 293 cells, the receptor exhibited high affinity (Kd = 2.8 nM) for 125I-labeled human pancreatic polypeptide (PP) [22].

Anatomical context of PPY

• Pancreatic polypeptide (PP) is produced in the islets of Langerhans and released in response to meals [23].
• Multiple forms of pancreatic polypeptide-related compounds in the lamprey CNS: partial characterization and immunohistochemical localization in the brain stem and spinal cord [24].
• Adjacent sections from the brain stem and spinal cord of L. fluviatilis and Ichthyomyzon unicuspis, incubated with the different antisera, displayed 2 main patterns of PP immunoreactivity [24].
• NPY is expressed exclusively in neurons, whereas PYY and PP are produced primarily in gut endocrine cells [25].
• All peptides display moderate binding affinities to neutral membranes (K(assoc) in the range of 1.7 to 6.8 x 10(4) mol(-)(1) as determined by surface plasmon resonance) with the differences in binding being most probably related to the exchange of Arg-19 (pNPY) by Glu-23 (hPP) [26].

Associations of PPY with chemical compounds

• Second, perturbation of the PP-fold by substitution with a helix-breaking proline residue, resulted in the loss of recognition of the N-terminal segment of the molecule by both types of receptors [27].
• This recently discovered human intestinal hormonal peptide thus has significant effects both on gastrointestinal hormones (motilin and pancreatic polypeptide) and blood pressure in man, but appears not to influence glucose or lipid metabolism [28].
• Intracerebroventricular administration of 2 or 10 micrograms of human pancreatic polypeptide to ovariectomized rats pretreated with estradiol benzoate plus progesterone significantly increased the number of animals feeding, and total food intake in tests conducted during the light phase of the day [6].
• 4. Y(1) receptor antagonists, BIBP3226 and BIBO3304 both increased basal I(sc) levels per se and inhibited subsequent PYY and Pro(34)PYY but not hPP or PYY(3 - 36) responses [29].
• In order to study the physiological significance of the coexistence of pancreatic polypeptide and norepinephrine (NE) in peripheral noradrenergic nerves, the effects of pancreatic polypeptides of several species were tested on the isolated rat vas deferens [30].

Physical interactions of PPY

• The antiparallel pancreatic polypeptide fold in the binding of neuropeptide Y to Y1 and Y2 receptors [27].
• Thus, the carboxyl-terminal region of PP seems to be the most important part of the peptide for high affinity binding to hPP1 [31].
• Endogenous CCK appears to interact with direct cholinergic stimulation at the pancreatic PP cell and the gastric D-cell but not at pancreatic acinar and antroduodenal smooth muscle cells [32].

Regulatory relationships of PPY

• Activation of extracellular signal regulated protein kinase by neuropeptide Y and pancreatic polypeptide in CHO cells expressing the NPY Y(1), Y(2), Y(4) and Y(5) receptor subtypes [33].
• Distension tended to increase integrated plasma PYY from 77 +/- 30 pM min to 128 +/- 40 pM min in the first hour after the meal (P = 0.08) and it suppressed integrated plasma PP from 1133 +/- 248 pM min to 269 +/- 284 pM min in the second hour (P < 0.05) [34].
• Atropine abolished secretory, motor, and pancreatic polypeptide responses to sham feeding and enhanced gastrin release [35].
• Effects of atropine on GIP-induced insulin and pancreatic polypeptide release in man [36].
• OBJECTIVE: Intravenously administered secretin stimulates pancreatic polypeptide (PP) release in patients with endocrine enteropancreatic tumors, but data in patients with nontumorous disorders are controversial [37].

Other interactions of PPY

• Gastrin concentrations were not modified, whereas significant rises were observed in both SS (in a biphasic pattern with peaks at 15 and 120 min) and PP (which increased promptly with a peak at 15 min) [38].
• PYY caused a significant 50% reduction in plasma pancreatic polypeptide concentrations (P less than 0.05) and a 55% reduction in circulating motilin levels (P less than 0.05) [28].
• In conclusion, this study clearly demonstrates that ghrelin stimulates SS and PP release in man [38].
• Pancreatic polypeptide (PP) potently displaced (125)I-1229U91 from the Y4 receptor, but displayed little affinity for Y1 [39].
• These altered sequences are accompanied by acquisition of new functions apparently unrelated to the neurotransmitter/endocrine role of PYY and PPY, as demonstrated by the major involvement of bovine PYY2, also known as seminal plasmin, in the fertilization process [20].

Analytical, diagnostic and therapeutic context of PPY

• A second weaker hybridization signal also found on chromosome 17q11 and results obtained by Southern blot analysis suggest that the entire PYY-PPY region has undergone a further duplication event [40].
• PP-like material was detected in extracts of brain and spinal cord from Lampetra fluviatilis by radioimmunoassay (RIA) using an antiserum to the C-terminal hexapeptide of mammalian PP [24].
• Members of the PP family regulate numerous physiological processes, including appetite, gastrointestinal transit, anxiety, and blood pressure [41].
• Immunofluorescence indicated that the Y4 receptor was not internalized within the cells after 24-h treatment with 10 nM hPP [2].
• This review considers the anorectic peptides PYY, PP, GLP-1, and oxyntomodulin, which decrease appetite and promote satiety in both animal models and humans [42].

References