The neuropeptide Y Y1 receptor selective radioligand, [125I][Leu31,Pro34]peptide YY, is also a high affinity radioligand for human pancreatic polypeptide 1 receptors

Gehlert, Donald R.; Gackenheimer, Susan L.; Schober, Douglas A.; Beavers, Lisa S.; Gadski, Robert A.; Burnett, J. Paul; Mayne, N.G.; Lundell, Ingrid; Larhammar, Dan

doi:10.1016/s0014-2999(96)00797-2

Cited by 26 publications

(18 citation statements)

References 9 publications

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“…The Y 4 subtype is characterized by its high affinity for PPs and GR231118 (as an agonist; Michel et al, 1998). The Leu 31 Pro 34 -substituted analogs of NPY and PYY are also potent agonists on the Y 4 subtype (Gehlert et al, 1996). This receptor subtype can be activated by PYY and NPY, but with much lower potencies than the PPs (Lundell et al, 1995 , and hPP display potent agonist activities, whereas NPY(13-36), PYY(13-36), rPP, and GR231118 are much less active (Michel et al, 1998;Dumont et al, 2004a (Cabrele et al, 2001).…”

Section: Resultsmentioning

confidence: 99%

“…These results were confirmed using the Y 5 receptor antagonist CGP71683A (Dumont et al, 2000a). However, under these assay conditions, the possible recognition of the Y 4 subtype could not be fully excluded because [Leu 31 ,Pro 34 ]PYY is known to possess nanomolar affinity for this receptor (Gehlert et al, 1996). It is interesting that, using purported Y 4 ligands such as 125 I-hPP, 125 I-rPP, and 125 I-labeled bovine PP, we were able to visualize a very discrete distribution of specific receptor sites with moderate to very high amounts seen in a few regions, including the medial preoptic area, paraventricular nucleus of the hypothalamus, and interpeduncular nucleus (Trinh et al, 1996;Gehlert et al, 1997).…”

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confidence: 91%

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Evidence for the Existence of an Additional Class of Neuropeptide Y Receptor Sites in Rat Brain

Dumont

Moyse²,

Fournier³

et al. 2005

J Pharmacol Exp Ther

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 91%

Evidence for the Existence of an Additional Class of Neuropeptide Y Receptor Sites in Rat Brain

Dumont

Moyse²,

Fournier³

et al. 2005

J Pharmacol Exp Ther

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“…Using [ 125 I]‐[Leu 31 ,Pro 34 ]‐PYY in the presence of selective non‐peptide Y 1 receptor antagonists, we were able to demonstrate that [ 125 I]‐[Leu 31 ,Pro 34 ]‐PYY/BIBP3226‐insensitive sites have a ligand binding profile similar to the Y 5 receptor subtype in the rat CNS (Dumont et al ., 1998a). However, under these conditions, the possible labelling of putative Y 4 receptor could not be fully excluded as [ 125 I]‐[Leu 31 ,Pro 34 ]‐PYY also possesses some affinity for this subtype (Gehlert et al ., 1996a). Interestingly, the present study demonstrated that [ 125 I]‐GR231118 binds with very high affinity to the Y 1 and Y 4 receptors, but not to the Y 2 and Y 5 subtypes, transfected in HEK293 cells.…”

Section: Discussionmentioning

confidence: 99%

“…However, none of the synthetic agonists used thus far demonstrated high selectivity for a single receptor subtype. In fact, [ 125 I]‐[Leu 31 ,Pro 34 ]‐PYY, first developed as a Y 1 agonist radioligand (Dumont et al ., 1995), was later demonstrated to bind with high affinity to the Y 4 (Gehlert et al ., 1996a,1996b; 1997) and Y 5 (Dumont et al ., 1998a; Gerald et al ., 1996) receptors. Similarly, [ 125 I]‐PYY 3–36 originally proposed as a Y 2 receptor probe (Dumont et al ., 1995) was found to also bind to the Y 5 (Gerald et al ., 1996) and possibly y 6 (Matsumoto et al ., 1996) subtypes.…”

Section: Introductionmentioning

confidence: 99%

[¹²⁵I]‐GR231118: a high affinity radioligand to investigate neuropeptide Y Y₁ and Y₄ receptors

Dumont

Quirion

2000

British J Pharmacology

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GR231118 (also known as 1229U91 and GW1229), a purported Y1 antagonist and Y4 agonist was radiolabelled using the chloramine T method. [125I]‐GR231118 binding reached equilibrium within 10 min at room temperature and remained stable for at least 4 h. Saturation binding experiments showed that [125I]‐GR231118 binds with very high affinity (Kd of 0.09–0.24 nM) in transfected HEK293 cells with the rat Y1 and Y4 receptor cDNA and in rat brain membrane homogenates. No specific binding sites could be detected in HEK293 cells transfected with the rat Y2 or Y5 receptor cDNA demonstrating the absence of significant affinity of GR231118 for these two receptor classes. Competition binding experiments revealed that specific [125I]‐GR231118 binding in rat brain homogenates is most similar to that observed in HEK293 cells transfected with the rat Y1, but not rat Y4, receptor cDNA. Autoradiographic studies demonstrated that [125I]‐GR231118 binding sites were fully inhibited by the Y1 antagonist BIBO3304 in most areas of the rat brain. Interestingly, high percentage of [125I]‐GR231118/BIBO3304‐insensitive binding sites were detected in few areas. These [125I]‐GR231118/BIBO3304‐insensitive binding sites likely represent labelling to the Y4 receptor subtype. In summary, [125I]‐GR231118 is a new radiolabelled probe to investigate the Y1 and Y4 receptors; its major advantage being its high affinity. Using highly selective Y1 antagonists such as BIBO3304 or BIBP3226 it is possible to block the binding of [125I]‐GR231118 to the Y1 receptor allowing for the characterization and visualization of the purported Y4 subtype. British Journal of Pharmacology (2000) 129, 37–46; doi:

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“…Because PYY has very low affinity for rat Y4, iodinated pancreatic polypeptide was used as a radioligand in its characterisation. The Y4 receptor has been extensively studied by different groups using both iodinated PYY, pancreatic polypeptide and LP-NPY (Gehlert et al 1996b, c, 1997, Gregor et al 1996, Voisin et al 2000, Parker et al 2001. Depending on the radioligand used, different affinities have been reported for the ligands in the various studies.…”

Section: Discussionmentioning

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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The neuropeptide Y Y1 receptor selective radioligand, [125I][Leu31,Pro34]peptide YY, is also a high affinity radioligand for human pancreatic polypeptide 1 receptors

Cited by 26 publications

References 9 publications

Evidence for the Existence of an Additional Class of Neuropeptide Y Receptor Sites in Rat Brain

Evidence for the Existence of an Additional Class of Neuropeptide Y Receptor Sites in Rat Brain

[¹²⁵I]‐GR231118: a high affinity radioligand to investigate neuropeptide Y Y₁ and Y₄ receptors

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

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The neuropeptide Y Y1 receptor selective radioligand, [125I][Leu31,Pro34]peptide YY, is also a high affinity radioligand for human pancreatic polypeptide 1 receptors

Cited by 26 publications

References 9 publications

Evidence for the Existence of an Additional Class of Neuropeptide Y Receptor Sites in Rat Brain

Evidence for the Existence of an Additional Class of Neuropeptide Y Receptor Sites in Rat Brain

[125I]‐GR231118: a high affinity radioligand to investigate neuropeptide Y Y1 and Y4 receptors

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

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[¹²⁵I]‐GR231118: a high affinity radioligand to investigate neuropeptide Y Y₁ and Y₄ receptors