Neuropeptide Y receptor subtype with unique properties cloned in the zebrafish: the zYa receptor

Starbäck, Paula; Lundell, Ingrid; Fredriksson, Robert; Berglund, Magnus; Yan, Yi‐Lin; Wraith, Amanda; Söderberg, Charlotte; Postlethwait, John H.; Larhammar, Dan

doi:10.1016/s0169-328x(99)00152-7

Cited by 44 publications

(26 citation statements)

References 47 publications

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“…94 The NPY cod, NPY Yb=zYb and NPY zYc receptors display NPY Y 1 -like pharmacology while the NPY zYa subtype seems to have a pharmacological profile closer to the NPY Y 5 receptor. 90 However, amino-acid sequence comparisons and phylogenetic analyses have shown that NPY zYb, zYc and zYa receptors are 48% 24% 36% 25% zYa 45% 27% 45% 26% 41% zYb 46% 26% 48% 22% 39% 48% zYc 45% 27% 49% 21% 41% 48% 73% LymNPY 22% 22% 21% 18% 23% 23% 24% 23% DroNPY 19% 22% 20% 19% 20% 22% 21% 19% 19% GPR74 25% 24% 23% 18% 25% 23% 22% 23% 18% 23% h, Human NPY receptor subtypes, z, zebra fish receptor subtypes; Lym, Lymneae stagnalis receptor subtype; Dro, Drosophilia receptor subtype, GPR 74, an orphan receptor with high binding affinity for PYY. 95,96 Appetite suppression S Chamorro et al not simple orthologues of existing mammalian NPY receptors.…”

Section: Npy Receptor Subtypesmentioning

confidence: 99%

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Appetite suppression based on selective inhibition of NPY receptors

Chamorro

Della‐Zuana

et al. 2002

Int J Obes

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AIM:The aim of this review is to critically assess available evidence that blockade of the actions of NPY at one of the five NPY receptor subtypes represents an attractive new drug discovery target for the development of an appetite suppressant drug. RESULTS: Blockade of the central actions of NPY using anti-NPY antibodies, antisense oligodeoxynucleotides against NPY and NPY receptor antagonists results in a decrease in food intake in energy-deprived animals. These results appear to show that endogenous NPY plays a role in the control of appetite. The fact that NPY receptors exist as at least five different subtypes raises the possibility that the actions of endogenous NPY on food intake can be adequately dissociated from other effects of the peptide. Current drug discovery has produced a number of highly selective NPY receptor antagonists which have been used to establish the NPY Y 1 receptor subtype as the most critical in regulating short-term food intake. However, additional studies are now needed to more clearly define the relative contribution of NPY acting through the NPY Y 2 and NPY Y 5 receptors in the complex sequence of physiological and behavioral events that underlie the long-term control of appetite. CONCLUSIONS: Blockade of the NPY receptor may produce appetite-suppressing drugs. However, it is too early to state with certainty whether a single subtype selective drug used alone or a combination of NPY receptor selective antagonists used in combination will be necessary to adequately influence appetite regulation.

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Section: Npy Receptor Subtypesmentioning

confidence: 99%

“…95,96 Appetite suppression S Chamorro et al not simple orthologues of existing mammalian NPY receptors. 90,91 In addition, neither the NPY receptors from Lymneae stagnalis nor Drosophila have counterparts in mammals. Therefore, it is possible that additional mammalian NPY receptors remain to be discovered.…”

Section: Npy Receptor Subtypesmentioning

confidence: 99%

Appetite suppression based on selective inhibition of NPY receptors

Chamorro

Della‐Zuana

et al. 2002

Int J Obes

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“…The broad pharmacological profile of the receptor is also reflected by the slightly greater affinities for pPYY and hPP over the corresponding endogenous peptides. The rather promiscuous pharmacological profile of the chY4 is reminiscent of the Ya receptor that was cloned in the zebrafish (Starback et al 1999). The zebrafish Ya receptor also binds truncated NPY analogues and the modified peptide LP-NPY with equal affinities.…”

Section: Discussionmentioning

confidence: 99%

“…The Y1 receptor differs from all other NPY receptor subtypes in that it has an intron in the coding region. In zebrafish, three distinct subtypes have been cloned: Ya, Yb and Yc , Ringvall et al 1997, Starback et al 1999. Their relationships to the mammalian receptors is unclear, but as each of them shares 45-50% identity to the Y1 subfamily receptors, they clearly belong to this subfamily.…”

Section: Introductionmentioning

confidence: 99%

Chicken neuropeptide Y-family receptor Y4: a receptor with equal affinity for pancreatic polypeptide, neuropeptide Y and peptide YY

Lundell

Boswell²,

Larhammar³

2002

Journal of Molecular Endocrinology

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Within the neuropeptide Y (NPY) family of peptides, pancreatic polypeptide is the most divergent across species. It differs in 20 of 36 positions between human and chicken. In mammals, it binds primarily to the Y4 receptor, to which NPY and peptide YY (PYY) bind with lower affinities. Because of these large sequence differences in pancreatic polypeptide, we decided to characterise the chicken Y4 receptor. We report here that Y4 displays the least sequence conservation among the Y-family receptors, with only 57-60% overall amino acid identity between chicken and mammals, compared with 64-83% for the Y1, Y2 and Y5 receptors. After expression of the chicken Y4 receptor in COS-7 cells, I-pPYY, chicken pancreatic polypeptide bound with high affinity at 140 pM. Interestingly, chicken PYY bound with even greater affinity at 68 pM. The affinity of NPY, 160 pM, was similar to that of pancreatic polypeptide. Chicken Y4 is less sensitive than is mammalian Y4 to truncation of the amino terminus of the NPY molecule. RT-PCR revealed expression in several peripheral organs, including adipose tissue and oviduct. In brain, Y4 mRNA was detected in the brainstem, cerebellum and hippocampus. In situ hybridisation to brain sections showed expression in the dorsal motor nucleus of the vagus in the brainstem. Thus the chicken Y4 receptor is less selective and anatomically more widespread than that in mammals, probably reflecting the original properties of the Y4 receptor.

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“…Prior to the initiation of these genome sequencing projects three Y1-like receptors had been cloned from zebrafish, but did not seem to represent orthologues to any of the mammalian Y1, Y4 or Y6 genes. These fish sequences were therefore tentatively regarded as novel genes and given distinct gene names, namely Ya, Yb and Yc [92,95,96]. As additional Y receptor sequences were reported, the relationships of these genes have become clearer.…”

Section: Figure 4 Proposed Gene Duplication Scheme For the Y Receptormentioning

confidence: 99%