CHARACTERIZATION OF Y-1, Y-2 AND Y-5 SUBTYPES OF THE NEUROPEPTIDE-Y (NPY) RECEPTOR IN RABBIT KIDNEY - SENSITIVITY OF LIGAND-BINDING TO GUANINE-NUCLEOTIDES AND PHOSPHOLIPASE-C INHIBITORS

The binding of two peptide YY/neuropeptide Y analogues selective for m ajor subtypes of neuropeptide Y (NPY) receptors was compared in partic ulates from rabbit kidney cortex employing modulators of activity of G -proteins, phospholipase enzymes, and ion channels. The binding of (Le u(31),Pro(34))human peptide YY resembled the patterns observed previou sly for the brain tissue Y-1 receptor, exhibiting a high sensitivity t o monovalent cations, disulfide disrupters, guanosine polyphosphates a nd phospholipase C inhibitors. However, this binding was bimodal in re sponse to human pancreatic polypeptide and to peptides selective for t he Y-2 subtype of the NPY receptor, displaying a large component pharm acologically similar to the brain Y-5 receptor. This kidney Y-5-like b inding largely shared the sensitivity to monovalent cations, guanine n ucleotides and phospholipase C inhibitors found for either the kidney or the brain Y-1 receptor, and also was activated by Ca2+ ion. Both Y- 1- and Y-5-like binding in the kidney displayed a uniformly low reacti vity to a nonpeptidic Y-1 antagonist, BIBP-3226, and to a receptor pep tide mimetic, mastoparan analogue MAS-7. The kidney Y-2 binding shared the low sensitivity to ionic environment observed for the brain Y-2 s ubtype, and was only partially sensitive to guanine nucleotides or to MAS-7. The Y-2 liganding had a sensitivity to phospholipase C inhibito rs similar to the Y-1/Y-5 binding. This reactivity was retained in the fraction of the Y-2 receptor persisting detergent solubilization in a high-affinity form, which, however, was activated rather than inhibit ed by G-protein agonists. (C) 1998 Elsevier Science B.V. All rights re served.