Novel generation of hormone receptor specificity by amino terminal processing of peptide YY

Grandt, Daniel; Teyssen, Stephan; Schimiczek, M.; Reeve, Joseph R.; Feth, Friedhelm; Rascher, Wolfgang; Hirche, Hans-Jürgen; Singer, Manfred V.; Layer, Peter; Goebell, H.; Ho, F.J.; Eysselein, Viktor E.

doi:10.1016/s0006-291x(05)81547-5

Cited by 81 publications

(55 citation statements)

References 8 publications

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“…Possible reasons for this difference in potency include differences in plasma clearance rates, access to target tissues (e.g., brain uptake), and receptor binding properties of the two PYY analogs. PYY and PYY appear to have similar plasma half-lives of 8 to 12 min in dogs (21,31,39). Plasma half-lives of PYY and PYY in rats, and the relative blood-brain barrier permeabilities of each peptide, remain to be determined.…”

Section: Discussionmentioning

confidence: 97%

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Chelikani

Haver²,

Reidelberger³

2004

American Journal of Physiology-Regulatory, Integrative and Comp

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We compared the effects of the two molecular forms of the brain-gut peptide YY (PYY), PYY(1-36) and PYY(3-36), on gastric emptying. Unanesthetized rats received 20-min intravenous infusions of rat PYY(1-36) (0, 1.7, 5, 17, 50, 100, 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) and rat PYY(3-36) (0, 0.5, 1.7, 5, 17, 50, 100, 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ), either alone or combined, and gastric emptying of saline was measured during the last 10 min of infusion. For comparison, human PYY(3-36) was administered at 0, 17, and 50 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 . Gastric emptying was decreased by 11, 24, 26 and 38% in response to 17, 50, 100, and 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 of rat PYY(1-36); by 10, 26, 41, 53, and 57% in response to 5, 17, 50, 100, and 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 of rat PYY(3-36); and by 35 and 53% in response to 17 and 50 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 of human PYY(3-36), respectively. Estimated ED50s were 470 and 37 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 for rat PYY(1-36) and PYY(3-36), respectively. In general, within an experiment, coadministration of PYY(1-36) and PYY(3-36) inhibited gastric emptying by an amount that was comparable to that produced when either peptide was given alone. We conclude that 1) intravenous infusion of PYY(1-36) and PYY(3-36) each produces a dose-dependent inhibition of gastric emptying in rats, 2) PYY(3-36) is an order of magnitude more potent than PYY(1-36) in inhibiting gastric emptying, 3) human PYY(3-36) and rat PYY(3-36) inhibit gastric emptying similarly, and 4) PYY(1-36) and PYY(3-36) do not appear to interact in an additive or synergistic manner to inhibit gastric emptying. intravenous infusion; dose response; interaction PEPTIDE YY (PYY), neuropeptide Y (NPY), and pancreatic polypeptide (PP) comprise the "PP-fold" family of structurally related brain-gut peptides. PYY is synthesized in the gastrointestinal tract, as well as in the central and peripheral nervous systems. Endocrine cells of the ileum, colon, and rectum provide a major source of PYY (2, 47). PYY has also been detected in gastric mucosa, pancreatic islets, myenteric and serosal ganglia, sympathetic neurons, adrenal gland, spinal cord, and brain, including the hypothalamus, pituitary, pons, medulla oblongata, and the brain stem (7-9, 15, 16, 22, 30, 32, 37).Food intake releases PYY into the circulation (2, 47). Systemic administration of PYY inhibits food intake, gastric emptying, intestinal fluid and electrolyte secretion, gallbladder contraction, and exocrine pancreatic secretion (5, 36). Whether PYY acts physiologically by endocrine, neurocrine, and/or paracrine mechanisms to produce these effects remains to be determined. If PYY acts as a blood-borne hormonal signal to produce an effect, then it is important to determine whether the effect is produced by intravenous doses of PYY that reproduce meal-induced increases in plasma PYY.The two major molecular forms of PYY found in the gut and circulation are PYY(1-36) and PYY(3-36) (19 -21). In humans, plasma concentrations of PYY were reported to be 11 pM in the fasted state with PYY(3-36) contributing 37% ...

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Section: Discussionmentioning

confidence: 97%

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Chelikani

Haver²,

Reidelberger³

2004

American Journal of Physiology-Regulatory, Integrative and Comp

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“…However, PYY accounts for only about 50% of total PYY immunoreactivity in postprandial human blood (20). The other major molecular form appears to be PYY(1-36) (20,21), which is an order of magnitude less potent than PYY in reducing food intake (10). Thus it remains to be determined whether PYY(3-36) acts as a blood-borne signal to decrease food intake in humans or rats.…”

Section: Discussionmentioning

confidence: 99%

“…4). During the subsequent 10-day treatment period, 1-h IV infusions of PYY(3-36) at 30 pmol⅐kg Ϫ1 ⅐min Ϫ1 significantly reduced food intake on successive days by 31,20,24,21,25,17,19,16,15 and 23%, respectively, compared with the vehicle-treated group (Figs. 4 and 5).…”

Section: Effects Of 1-h IV Infusions Of Pyy(3-36) Every Other Hour Onmentioning

confidence: 95%

Daily, intermittent intravenous infusion of peptide YY(3-36) reduces daily food intake and adiposity in rats

Chelikani

Haver²,

Reeve³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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reduces food intake and weight gain in rats when injected into the peritoneal cavity twice daily for 7 days. Numerous laboratories have failed to confirm that daily injections of PYY(3-36) decrease body weight. Continuous subcutaneous administration of PYY(3-36) by osmotic minipump has been reported to reduce daily food intake in rodents but only during the first 3-4 days of administration. Here we show the effects of different daily patterns of intravenous infusion of PYY(3-36) on food intake, body weight, and adiposity in rats tethered via infusion swivels to computercontrolled pumps. Measurement of food bowl weight recorded by computer every 20 s permitted daily assessment of the instantaneous effects of PYY(3-36) administration on food intake and meal patterns. One-hour intravenous infusions of PYY(3-36) at 30 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 every other hour for 10 days produced a sustained reduction in daily food intake of ϳ20% and decreased body weight and adiposity by 7 and 35%, respectively. Thus dosage pattern is critical for producing a sustained effect of PYY(3-36) on food intake and adiposity.gastrointestinal; body weight; body composition THE GASTROINTESTINAL SYSTEM plays an important sensing and signaling role in control of food intake and regulation of energy reserves (5). A growing number of peptide signals of gastric, intestinal, and pancreatic origin have been shown to inhibit short-term food intake when administered acutely to experimental animals and humans. These include cholecystokinin, amylin, glucagon-like peptide-1 (GLP-1), oxyntomodulin, peptide YY(3-36) ], pancreatic polypeptide, gastrinreleasing peptides (GRPs) GRP-27 and GRP-

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“…Two forms of PYY are found in the gut and circulation: PYY and PYY [9][10][11]. Batterham et al provided the first evidence that PYY is a mediator of postprandial satiety in rodents [6] and humans [12] through actions at the arcuate nucleus via NPY2 receptor (NPY2R).…”

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects

et al. 2007

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Aims/hypothesis Genetic variants of genes for peptide YY (PYY), neuropeptide Y2 receptor (NPY2R) and pancreatic polypeptide (PPY) were investigated for association with severe obesity. Subjects and methods The initial screening of the genes for variants was performed by sequencing in a group of severely obese subjects (n=161). Case-control analysis of the common variants was then carried out in 557 severely obese adults, 515 severely obese children and 1,163 nonobese/non-diabetic control subjects. Rare variants were genotyped in 700 obese children and the non-obese/nondiabetic control subjects (n=1,163). Results Significant association was found for a 5′ variant (rs6857715) in the NPY2R gene with both severe adult obesity (p=0.002) and childhood obesity (p=0.02). This significant association was further supported by a pooled allelic analysis of all obese cases (adults and children, n=928) vs the control subjects (n=938) (p=0.0004, odds ratio=1.3, 95% CI 1.1-1.5). Quantitative trait analysis of BMI and WHR was performed and significant association was observed for SNP rs1047214 in NPY2R with an increase in WHR in the severely obese children (codominant model p=0.005, recessive model p=0.001). Association was also observed for an intron 3 variant (rs162430) in the PYY gene with childhood obesity (p=0.04). No significant associations were observed for PPY variants. Only one rare variant in the NPY2R gene (C-5641T) was not found in lean individuals and this was found to co-segregate with obesity in one family. Conclusions/interpretation These results provide evidence of association for NPY2R and PYY gene variants with obesity and none for PPY variants. A rare variant of the NPY2R gene showed evidence of co-segregation with Diabetologia (2007)

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Novel generation of hormone receptor specificity by amino terminal processing of peptide YY

Cited by 81 publications

References 8 publications

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Daily, intermittent intravenous infusion of peptide YY(3-36) reduces daily food intake and adiposity in rats

Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects

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