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 p roximal tubule cell line, derived from transgenic mice (SV40 large T a ntigen under the control of the rat L-type pyruvate kinase 5'-regulato ry sequence). Binding of [I-125-Tyr36]monoiodo-PYY ([I-125] PYY to cel l was specific, saturable, and reversible. The order of potency for pe ptides for inhibiting [I-125]PYY binding was: PYY > neuropeptide Y (NP Y) = PYY(13-36) >> pancreatic polypeptide. A single class of receptors was observed with a K(d) of 0.37 +/- 0.05 nm and a B(max) of 103 +/- 10 fmol/mg protein. After cross-linking, electrophoresis of covalent [ I-125]pyy-receptor complexes revealed a single band of M(r) 50,000. PY Y receptors were exclusively present at the basolateral membrane surfa ce of polarized cells and were coupled negatively to adenylylcyclase b y a pertussis toxin-sensitive G protein. PKSV-PCT cell growth and T an tigen expression could be modulated by D-glucose in the medium. PYY re ceptors 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 b y reintroduction of D-glucose. PYY stimulated cell growth (17-26% incr ease) and promoted [methyl-H-3]thymidine incorporation into DNA (64% i ncrease; ED50 = 5 nM PYY) of cells grown in D-glucose-enriched medium. This latter effect of PYY was largely reversed by pretreatment of cel ls with pertussis toxin. These findings suggest that PYY receptors pla y a role in epithelial cell growth.