Linked Life Data

10734179

Source:http://linkedlifedata.com/resource/pubmed/id/10734179

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-4-21
pubmed:abstractText
1229U91 (GW1229 or GR231118) [lle,Glu,Pro,Dpr,Tyr, Arg,Leu,Arg, Tyr-NH(2))2 cyclic (2,4'),(2'4)-diamide] has been reported by several research groups to be a potent antagonist at the Y1 neuropeptide Y (NPY) receptor subtype. However, 1229U91 also displaces (125)I-peptide YY (PYY) with high affinity from the Y4 subtype. Previously, we reported that 1229U91 had full agonist properties for the Y4 receptor. To characterize the pharmacological properties of 1229U91 directly, we had it radioiodinated with the chloromine-T method. (125)I-1229U91 bound to cell lines expressing the human Y1 and Y4 receptors with high affinity. The K(d) and B(max) for (125)I-1229U91 binding to Y1 were 14.9 pM and 1458 fmol/mg protein, respectively. The Y4 receptor bound (125)I-1229U91 with a K(d) of 12.5 pM and a B(max) of 1442 fmol/mg protein. When competing (125)I-1229U91 binding from Y1 and Y4 receptors, a similar rank order of potency was observed: 1229U91 > [Leu(31),Pro(34)]-NPY >/= [Leu(31),Pro(34)]-PYY > PYY >/= NPY > NPY(2-36) > PYY(3-36). Pancreatic polypeptide (PP) potently displaced (125)I-1229U91 from the Y4 receptor, but displayed little affinity for Y1. In autoradiographic studies with rat brain sections, (125)I-1229U91 bound with a distribution similar to that reported for the Y1 receptor when localized with (125)I-[Leu(31),Pro(34)]-PYY. Brain regions exhibiting binding sites for (125)I-PP were not detected with this radioligand. Those include the interpeduncular nucleus and the periventricular nucleus of the hypothalamus. Furthermore, (125)I-labeled rat PP was not displaced from these areas with 10 nM 1229U91. Thus, (125)I-1229U91 is a high affinity Y1 and Y4 radioligand and binds with a distribution in the rat brain consistent with the localization of the Y1 receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
293
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
275-80
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10734179-Animals, pubmed-meshheading:10734179-Autoradiography, pubmed-meshheading:10734179-Binding, Competitive, pubmed-meshheading:10734179-Brain Chemistry, pubmed-meshheading:10734179-CHO Cells, pubmed-meshheading:10734179-Cloning, Molecular, pubmed-meshheading:10734179-Cricetinae, pubmed-meshheading:10734179-Humans, pubmed-meshheading:10734179-Iodine Radioisotopes, pubmed-meshheading:10734179-Kinetics, pubmed-meshheading:10734179-Male, pubmed-meshheading:10734179-Membranes, pubmed-meshheading:10734179-Neuropeptide Y, pubmed-meshheading:10734179-Neuropeptides, pubmed-meshheading:10734179-Pancreatic Polypeptide, pubmed-meshheading:10734179-Peptides, Cyclic, pubmed-meshheading:10734179-Rats, pubmed-meshheading:10734179-Rats, Sprague-Dawley, pubmed-meshheading:10734179-Receptors, Neuropeptide Y
pubmed:year
2000
pubmed:articleTitle
Pharmacological characterization of (125)I-1229U91 binding to Y1 and Y4 neuropeptide Y/Peptide YY receptors.
pubmed:affiliation
Lilly Neuroscience, Lilly Research Laboratories, Eli Lilly and Co., Lilly Corporate Center, Indianapolis, Indiana, USA.
pubmed:publicationType
Journal Article, In Vitro