Source:http://linkedlifedata.com/resource/pubmed/id/16807358
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2006-9-26
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pubmed:abstractText |
The antisecretory effects of several Y agonists, including pancreatic polypeptide (PP), indicate the presence of Y(1), Y(2), and Y(4) receptors in mouse and human (h) colon mucosae. Here, we used preparations from human and from wild-type (WT), Y(4), and Y(1) receptor knockout ((-/-)) mice, alongside Y(4) receptor-transfected cells to define the relative functional contribution of the Y(4) receptor. First, rat (r) PP antisecretory responses were lost in murine Y(4)(-/-) preparations, but hPP and Pro(34) peptide YY (PYY) costimulated Y(4) and Y(1) receptors in WT mucosa. The Y(1) antagonist/Y(4) agonist GR231118 [(Ile,Glu,Pro,Dpr,Tyr,Arg,Leu,Arg,Try-NH(2))-2-cyclic(2,4'),(2',4)-diamide] elicited small Y(4)-mediated antisecretory responses in human tissues pretreated with the Y(1) antagonist, BIBO3304 [(R)-N-[[4-(aminocarbonylaminomethyl)-phenyl]methyl]-N(2)-(diphenylacetyl)-argininamide trifluoroacetate)], and attenuated Y(4)-mediated hPP responses in mouse and human mucosa. GR231118 and rPP were also antisecretory in hY(4)-transfected epithelial monolayers but were partial agonists compared with hPP at this receptor. In Y(4)-transfected human embryonic kidney (HEK) 293 cells, Y(4) ligands displaced [(125)I]hPP binding with orders of affinity (pK(i)) at human (hPP = rPP > GR231118 > Pro(34)PYY = PYY) and mouse (rPP = hPP > GR231118 > Pro(34)PYY > PYY) Y(4) receptors. GR231118- and rPP-stimulated guanosine 5'-3-O-(thio)triphosphate binding through hY(4) receptors with significantly lower efficacy than hPP. GR231118 marginally increased basal but abolished further PP-induced hY(4) internalization to recycling (transferrin-labeled) pathways in HEK293 cells. Taken together, these findings show that Y(4) receptors play a definitive role in attenuating colonic anion transport and may be useful targets for novel antidiarrheal agents due to their limited peripheral expression.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1229U91,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine 5'-O-(3-Thiotriphosphate),
http://linkedlifedata.com/resource/pubmed/chemical/Pancreatic Polypeptide,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides, Cyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neuropeptide Y,
http://linkedlifedata.com/resource/pubmed/chemical/neuropeptide Y4 receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
319
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
20-30
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16807358-Amino Acid Sequence,
pubmed-meshheading:16807358-Animals,
pubmed-meshheading:16807358-Colon,
pubmed-meshheading:16807358-Guanosine 5'-O-(3-Thiotriphosphate),
pubmed-meshheading:16807358-Humans,
pubmed-meshheading:16807358-Intestinal Mucosa,
pubmed-meshheading:16807358-Mice,
pubmed-meshheading:16807358-Mice, Inbred C57BL,
pubmed-meshheading:16807358-Molecular Sequence Data,
pubmed-meshheading:16807358-Pancreatic Polypeptide,
pubmed-meshheading:16807358-Peptides, Cyclic,
pubmed-meshheading:16807358-Rats,
pubmed-meshheading:16807358-Receptors, Neuropeptide Y,
pubmed-meshheading:16807358-Species Specificity
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pubmed:year |
2006
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pubmed:articleTitle |
Y(4) receptors mediate the inhibitory responses of pancreatic polypeptide in human and mouse colon mucosa.
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pubmed:affiliation |
Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London SE1 1UL, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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