Peptide YY receptors in the proximal tubule PKSV-PCT cell line derived from transgenic mice. Relation with cell growth.
Receptors for peptide YY (PYY) were identified in the PKSV-PCT renal proximal tubule cell line, derived from transgenic mice (SV40 large T antigen under the control of the rat L-type pyruvate kinase 5'-regulatory sequence). Binding of [125I-Tyr36]monoiodo-PYY ([125I] PYY to cell was specific, saturable, and reversible. The order of potency for peptides for inhibiting [125I]PYY binding was: PYY > neuropeptide Y (NPY) = PYY (13-36) >> pancreatic polypeptide. A single class of receptors was observed with a Kd of 0.37 +/- 0.05 nM and a Bmax of 103 +/- 10 fmol/mg protein. After cross-linking, electrophoresis of covalent [125I]PYY-receptor complexes revealed a single band of M(r) 50,000. PYY receptors were exclusively present at the basolateral membrane surface of polarized cells and were coupled negatively to adenylylcyclase by a pertussis toxin-sensitive G protein. PKSV-PCT cell growth and T antigen expression could be modulated by D-glucose in the medium. PYY receptors were exclusively expressed in proliferative cells cultured in the presence of D-glucose. PYY receptors disappeared in the absence of D-glucose and were expressed again when proliferation was activated by reintroduction of D-glucose. PYY stimulated cell growth (17-26% increase) and promoted [methyl-3H]thymidine incorporation into DNA (64% increase; ED50 = 5 nM PYY) of cells grown in D-glucose-enriched medium. This latter effect of PYY was largely reversed by pretreatment of cells with pertussis toxin. These findings suggest that PYY receptors play a role in epithelial cell growth.
Unité de Biologie et Physiologie des Cellules Digestives, Institut National de la Santé et de la Recherche Médicale, Unité 239, Paris, France.
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Voisin
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Bens
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Cluzeaud
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Vandewalle
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Laburthe
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D019204:GTP-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism; D005768:Gastrointestinal Hormones / Q000378:metabolism; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D008970:Molecular Weight; D019894:Peptide YY; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D011770:Pyruvate Kinase / Q000235:genetics; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone; D012045:Regulatory Sequences, Nucleic Acid; D013539:Simian virus 40 / Q000235:genetics; D013936:Thymidine / Q000378:metabolism
D000952:Antigens, Polyomavirus Transforming; D005768:Gastrointestinal Hormones; D010455:Peptides; D011956:Receptors, Cell Surface; D011964:Receptors, Gastrointestinal Hormone; C082172:peptide YY receptor; D019894:Peptide YY; D005576:Colforsin; D004247:DNA; D000242:Cyclic AMP; D011770:Pyruvate Kinase; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D005947:Glucose; D013936:Thymidine