Characterization of rabbit kidney and brain pancreatic polypeptide-binding neuropeptide Y receptors: differences with Y1 and Y2 sites in sensitivity to amiloride derivatives affecting sodium transport.
Sites sensitive to human and rat pancreatic polypeptides (hPP and rPP) accounted for more than 30% of the specific binding of [125I](Leu31,Pro34) human peptide YY (LP-PYY) in particulates from rabbit kidney cortex, and about 10% of the specific binding in membranes from rabbit hypothalamus. The binding of [125I]hPP or [125I]rPP showed a high-affinity displacement with either hPP, rPP, LP-PYY, neuropeptide Y or peptide YY (Ki below 50 pM for all), while being quite insensitive to Y2-selective ligands. The PP binding had a high sensitivity to alkali cations and inhibitors of phospholipase C, very similar to that of LP-PYY binding 'masked' by excess cold hPP. However, as different from the Y1-like LP-PYY binding, but similar to the binding of the Y2-selective ligand [125I]human peptide YY(3-36) (hPYY(3-36)), the PP binding showed a low sensitivity to guanosine polyphosphates. The PP binding was much more sensitive to N5-substituted amiloride inhibitors of Na+ transport than the binding of LP-PYY, or that of hPYY(3-36). The inhibition of PP binding by N5-substituted amilorides was not enhanced by guanine nucleotides or by phospholipase C blockers. However, pairing of N5-substituted amilorides disproportionately increased the inhibition of hPP binding. Thus, in rabbit kidney or hypothalamus, the high-affinity PP-responding sites share some of the basic properties of the Y1 and Y2 sites, but are distinguished from both by a high sensitivity to compounds affecting sodium transport. These PP/NPY receptors could associate with membrane structures involved in the control of ion balance and osmotic responses.
Parker
S L
SL
Department of Pharmacology, University of Tennessee College of Medicine, Memphis 38163, USA. slparker@utmem1.utmem.edu
Parker
M S
MS
Crowley
W R
WR
D000584:Amiloride / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002414:Cations, Monovalent / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D007457:Iodine Radioisotopes; D017136:Ion Transport / Q000187:drug effects; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000378:metabolism*; D009636:Norbornanes; D010191:Pancreatic Polypeptide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019894:Peptide YY / Q000037:antagonists & inhibitors / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D016415:Sequence Alignment; D012964:Sodium / Q000378:metabolism; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D001952:Bridged-Ring Compounds; D002414:Cations, Monovalent; D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D009478:Neuropeptide Y; D009636:Norbornanes; D010726:Phosphodiesterase Inhibitors; D018013:Receptors, Neuropeptide; D013859:Thiocarbamates; D013871:Thiones; D019894:Peptide YY; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010191:Pancreatic Polypeptide; C046498:tricyclodecane-9-yl-xanthogenate; D000584:Amiloride; D012964:Sodium; D010738:Type C Phospholipases; D011796:Quinacrine