RT Journal Article
SR Electronic
T1 Characterization of G Protein and Phospholipase C-Coupled Agonist Binding to the Y<sub>1</sub> Neuropeptide Y Receptor in Rat Brain: Sensitivity to G Protein Activators and Inhibitors and to Inhibitors of Phospholipase C
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JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 382
OP 391
VO 286
IS 1
A1 Steven L. Parker
A1 Michael S. Parker
A1 Trevor Sweatman
A1 William R. Crowley
YR 1998
UL http://jpet.aspetjournals.org/content/286/1/382.abstract
AB Binding of a Y1-subtype-selective agonist of neuropeptide Y (NPY) receptor, (Leu31,Pro34)human peptide YY (LP-PYY), to particulates from four rat brain areas (parietal cortex area 1, piriform cortex, anterior hypothalamus and hippocampus) showed a distinct response to LP-PYY and PYY, a uniformly low sensitivity to ligands selective for the Y2, Y4 and Y5 NPY receptor subtypes and high sensitivity to a Y1 site-selective antagonist, BIBP-3226. The Y1binding was sensitive to guanine nucleotide-binding protein (G protein) agonist and antagonist nucleotides, with the rank order of guanosine 5′-O-(thiotriphosphate) (GTPγS) &gt; GTP &gt; GDP &gt; guanosine 5′-O-(thiodiphosphate). However, guanine nucleotides did not affect about one third of the specific Y1 binding. Most of Y1 binding could be inhibited by a G protein nucleotide site/docking site receptor mimic, mastoparan analog MAS-7. In all areas examined, the Y1 binding of LP-PYY was little affected by up to 100 μM of the antagonists of K+, Na+and Ca++ channels, protein kinase C, phospholipase A2, phospholipase D and phosphatidylinositol 3-kinase, phospholipase substrate phospholipids, steroids or detergents. However, the binding was potently inhibited by phospholipase C inhibitors (especially the aminosteroid U-73122), which also dissociated the bound Y1 ligand in steady-state conditions. U-73122 also displaced the Y1 binding insensitive to GTPγS. Ligand association with the brain Y1 NPY receptor thus strongly depends on activity of both G proteins and phospholipase C, implying specific interactions of these transducers/effectors with the receptor molecule in ligand binding. A portion of brain Y1 sites could be directly coupled to phospholipase(s) C. The American Society for Pharmacology and Experimental Therapeutics