[Pro34]peptide YY is a Y1-selective agonist at peptide YY/neuropeptide Y receptors.
We have investigated binding and functional effects of a new peptide YY analogue, [Pro34]peptide YY, at Y1 and Y2-like subtypes of receptors for peptide YY and neuropeptide Y. In binding studies [Pro34]peptide YY had a similarly high affinity as peptide YY to human Y1-like receptors in SK-N-MC cells, a human neuroblastoma cell line of presumed neurogenic origin, and HEL cells, a human cell line derived from a patient with Hodgkin's disease. In functional studies [Pro34]peptide YY stimulated Ca2+ elevations in both Y1-like receptor cell lines with similar potency and efficacy as peptide YY. In contrast to peptide YY [Pro34]peptide YY was 1000-fold less potent in binding to Y2-like receptors in porcine splenic membranes and lacked agonistic effects in another Y2-like receptor-mediated model system, i.e. inhibition of [3H]serotonin release from rat cerebral cortical slices. Thus, [Pro34]peptide YY is a highly Y1-selective full agonist of peptide YY/neuropeptide Y receptors. [Pro34]peptide YY could be useful for studying the importance of Y receptor subtypes in mediating peptide YY physiological actions.
Department of Gastroenterology, University of Essen, Germany.
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D
Grandt
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Feth
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Rascher
J R
JR
Reeve
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Schlicker
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Schimiczek
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Layer
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Goebell
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Eysselein
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Michel
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001932:Brain Neoplasms / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006689:Hodgkin Disease / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000378:metabolism; D019894:Peptide YY; D010455:Peptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists* / Q000096:biosynthesis / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013552:Swine; D014407:Tumor Cells, Cultured
D010455:Peptides; D011964:Receptors, Gastrointestinal Hormone; C082172:peptide YY receptor; C091928:peptide YY, Pro(34)-; D019894:Peptide YY; D012701:Serotonin; D002118:Calcium