Characterization of Y1, Y2 and Y5 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 major subtypes of neuropeptide Y (NPY) receptors was compared in particulates from rabbit kidney cortex employing modulators of activity of G-proteins, phospholipase enzymes, and ion channels. The binding of (Leu31,Pro34)human peptide YY resembled the patterns observed previously for the brain tissue Y1 receptor, exhibiting a high sensitivity to monovalent cations, disulfide disruptors, guanosine polyphosphates and phospholipase C inhibitors. However, this binding was bimodal in response to human pancreatic polypeptide and to peptides selective for the Y2 subtype of the NPY receptor, displaying a large component pharmacologically similar to the brain Y5 receptor. This kidney Y5-like binding largely shared the sensitivity to monovalent cations, guanine nucleotides and phospholipase C inhibitors found for either the kidney or the brain Y1 receptor, and also was activated by Ca2+ ion. Both Y1- and Y5-like binding in the kidney displayed a uniformly low reactivity to a nonpeptidic Y1 antagonist, BIBP-3226, and to a receptor peptide mimetic, mastoparan analogue MAS-7. The kidney Y2 binding shared the low sensitivity to ionic environment observed for the brain Y2 subtype, and was only partially sensitive to guanine nucleotides or to MAS-7. The Y2 liganding had a sensitivity to phospholipase C inhibitors similar to the Y1/Y5 binding. This reactivity was retained in the fraction of the Y2 receptor persisting detergent solubilization in a high-affinity form, which, however, was activated rather than inhibited by G-protein agonists.
Parker
S L
SL
Department of Pharmacology, University of Tennessee School of Medicine, Memphis 38163, USA. slparker@utmem1.utmem.edu
Parker
M S
MS
Crowley
W R
WR
D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000378:metabolism*; D008024:Ligands; D008297:Male; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000378:metabolism; D011817:Rabbits; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D000477:Alkylating Agents; D004791:Enzyme Inhibitors; D006150:Guanine Nucleotides; D008024:Ligands; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; C100568:neuropeptide Y5 receptor; D010738:Type C Phospholipases