Identification and Distribution of mRNA Encoding the Y1, Y2, Y4, and Y5 Receptors for Peptides of the PP-fold Family in the Rat Intestine and Colon

Goumain, Mathieu; Voisin, Thierry; Lorinet, Anne-Marie; Laburthe, Marc

doi:10.1006/bbrc.1998.8647

Cited by 97 publications

(71 citation statements)

References 27 publications

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“…8,12,24 Y2R is highly expressed in the arcuate nucleus, a major integrator of appetite control in the hypothalamus, but also in other hypothalamic areas, dorsal root ganglia, hippocampus, as well as in peripheral neurons, the intestine and certain blood vessels. [25][26][27][28] Y2R mediates presynaptic actions involving suppression of neurotransmitter release 29 through inhibition of adenylyl activation via Gi. 25 It is expressed mainly in orexigenic NPY/AGRP neurons 15 which, in direct synaptic contact with anorectic POMC/CART neurons in the arcuate nucleus, 30 integrates gut hormone signals such as PYY .…”

Section: Discussionmentioning

confidence: 99%

“…[25][26][27][28] Y2R mediates presynaptic actions involving suppression of neurotransmitter release 29 through inhibition of adenylyl activation via Gi. 25 It is expressed mainly in orexigenic NPY/AGRP neurons 15 which, in direct synaptic contact with anorectic POMC/CART neurons in the arcuate nucleus, 30 integrates gut hormone signals such as PYY . 31,32 Hence, Y2R mediates negative regulation of NPY signaling, and indirectly upregulation of POMC/CART, through PYY and NPY.…”

Section: Discussionmentioning

confidence: 99%

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Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men

et al. 2005

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Background: Gut hormones and their receptors are considered important in the control of feeding behavior. The gut hormone peptide-YY (PYY) has anorexic effects via the inhibitory neuropeptide Y2 receptor (Y2R) highly expressed in orexigenic NPY/ AGRP neurons within the arcuate nucleus, a major integrator of appetite control in the hypothalamus. Design: Genetic case-control association study of single nucleotide polymorphisms (SNPs) in Y2R and PYY. Subjects: Swedish Caucasians comprising 148 lean, 129 overweight/obese and 226 morbidly obese men. Measurements: Genotypes of the common, silent and conserved SNP Y2R 585T4C and the common SNP PYY Arg72Thr, as well as various obesity-related clinical parameters. Results: Obese men had a lower allele and homozygosity frequency of the common allele 585T4C:T which was particularly evident comparing morbidly obese with lean men (P ¼ 0.002), and analyzing dependence between continuous body mass index (BMI) and genotype (P ¼ 0.002). In agreement, systolic blood pressure tended to be lower in those homozygous for allele T, which was not explained by the BMI -genotype dependence. We found no association to obesity for the PYY Arg72Thr polymorphism, which is located nearby the essential carboxy terminal. Conclusion: A common and conserved variant of the PYY and NPY receptor Y2R is less prevalent among obese compared to among lean Swedish men. This suggests that the common Y2R variant is protective against obesity. Our findings further implicate Y2R in food intake regulation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men

et al. 2005

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“…In addition to this central mechanism, it is also possible that PYY(3-36) interacts directly with Y 2 receptors along the gastrointestinal tract to decrease gastric emptying. The mRNA for Y 2 receptors has been detected in the intestine of rats (18), and activation of colonic Y 2 receptors has been reported to increase longitudinal smooth muscle tone in human and mouse colon (24). In addition to these possible endocrine mechanisms, the presence of PYY immunoreactivity in the gastric mucosa and enteric nervous system (15) suggests that PYY(3-36) might also act by paracrine or neurocrine mechanisms to inhibit gastric emptying.…”

Section: Discussionmentioning

confidence: 99%

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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“…[27][28][29][30] Peripheral Y1-receptor signalling could, therefore, conceivably be involved in the regulation of energy balance, as is the case for peripheral Y2 receptors. 31 Although pharmacological studies with central administration of NPY and/or Y1 ligands have established a function of central Y1 receptors in mediating NPY's effects on food intake, 15,32,33 little is known about the function of peripherally expressed Y1 receptors in the regulation of energy homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Peripheral neuropeptide Y Y1 receptors regulate lipid oxidation and fat accretion

et al. 2009

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Objective: Neuropeptide Y and its Y receptors are important players in the regulation of energy homeostasis. However, while their functions in feeding regulation are well recognized, functions in other critical aspects of energy homeostasis are largely unknown. To investigate the function of Y1 receptors in the regulation of energy homeostasis, we examined energy expenditure, physical activity, body composition, oxidative fuel selection and mitochondrial oxidative capacity in germline Y1 À/À mice as well as in a conditional Y1-receptor-knockdown model in which Y1 receptors were knocked down in peripheral tissues of adult mice. Results: Germline Y1À/À mice of both genders not only exhibit a decreased respiratory exchange ratio, indicative of increased lipid oxidation, but interestingly also develop late-onset obesity. However, the increased lipid oxidation is a primary effect of Y1 deletion rather than secondary to increased adiposity, as young Y1 À/À mice are lean and show the same effect. The mechanism behind this is likely because of increased liver and muscle protein levels of carnitine palmitoyltransferase-1 (CPT-1) and maximal activity of key enzymes involved in b-oxidation; b-hydroxyacyl CoA dehydrogenase (bHAD) and medium-chain acyl-CoA dehydrogenase (MCAD), leading to increased mitochondrial capacity for fatty acid transport and oxidation. These effects are controlled by peripheral Y1-receptor signalling, as adult-onset conditional Y1 knockdown in peripheral tissues also leads to increased lipid oxidation, liver CPT-1 levels and bHAD activity. Importantly, these mice are resistant to diet-induced obesity. Conclusions: This work shows the primary function of peripheral Y1 receptors in the regulation of oxidative fuel selection and adiposity, opening up new avenues for anti-obesity treatments by targeting energy utilization in peripheral tissues rather than suppressing appetite by central effects.

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Identification and Distribution of mRNA Encoding the Y1, Y2, Y4, and Y5 Receptors for Peptides of the PP-fold Family in the Rat Intestine and Colon

Cited by 97 publications

References 27 publications

Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men

Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men

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

Peripheral neuropeptide Y Y1 receptors regulate lipid oxidation and fat accretion

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