Characterization of rabbit kidney and brain pancreatic polypeptide-bindingneuropeptide Y receptors: differences with Y-1 and Y-2 sites in sensitivity to amiloride derivatives affecting sodium transport

Sites sensitive to human and rat pancreatic polypeptides (hPP and rPP) acco unted for more than 30% of the specific binding of [I-125](Leu(31),Pro(34)) human peptide YY (LP-PYY) in particulates from rabbit kidney cortex, and a bout 10% of the specific binding in membranes from rabbit hypothalamus. The binding of [I-125]hPP or [I-125]rPP showed a high-affinity displacement wi th either hPP, rPP, LP-PYY, neuropeptide Y or peptide YY (K-i below 50 pM f or all), while being quite insensitive to Y-2 selective ligands. The PP bin ding had a high sensitivity to alkali cations and inhibitors of phospholipa se C, very similar to that of LP-PYY binding 'masked' by excess cold hPP. H owever, as different from the Y-1-like LP-PYY binding, but similar to the b inding of the Y-2-selective ligand [I-125] human peptide YY(3-36) (hPYY(3-3 6)), the PP binding showed a low sensitivity to guanosine polyphosphates. T he PP binding was much more sensitive to NS-substituted amiloride inhibitor s of Na+ transport than the binding of LP-PYY, or that of hPYY(3-36). The i nhibition of PP binding by NS-substituted amilorides was not enhanced by gu anine nucleotides or by phospholipase C blockers. However, pairing of N5-su bstituted amilorides disproportionately increased the inhibition of hPP bin ding. Thus, in rabbit kidney or hypothalamus, the high-affinity PP-respondi ng sites share some of the basic properties of the Y-1 and Y-2 sites, but a re distinguished from both by a high sensitivity to compounds affecting sod ium transport. These PP/NPY receptors could associate with membrane structu res involved in the control of ion balance and osmotic responses. (C) 1999 Elsevier Science B.V. All rights reserved.