Differences in cation sensitivity of ligand binding to Y1 and Y2 subtype of neuropeptide Y receptor of rat brain.
The binding of selective ligands to the Y1 subtype of neuropeptide Y receptor in rat brain particulates was promoted by Ca2+ and also stimulated by Sr2+, but reversibly reduced by Ba2+, Mg2+, Mn2+, by the organic polycations neomycin and spermidine, and by chelating agents. The alkali monovalent cations inhibited the Ca(2+)-enabled Y1 subtype binding with some selectivity (Cs+ > or = NH4+ > Li+ > Na+, K+), with half-inhibition between 70-120 mM. The specific Y2 subtype binding was enhanced by all alkaline-earth divalent cations, Mn2+, neomycin and spermidine in the range of 0.1-10 mM, and by alkali cations at up to 100 mM, and also by Na+ salts of the chelators EGTA and EDTA. The large disparity in cation sensitivity indicates substantial differences in the structure of the binding sites of the Y1 and Y2 receptors, predictable from known distinct features of ligand epitopes and of primary structure of the receptors.
Parker
M S
MS
Department of Pharmacology, University of Tennessee College of Medicine, Memphis, USA.
Crowley
W R
WR
Parker
S L
SL
D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D002414:Cations, Monovalent / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D009355:Neomycin / Q000494:pharmacology; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D013095:Spermidine / Q000494:pharmacology
D002413:Cations, Divalent; D002414:Cations, Monovalent; D002614:Chelating Agents; D008024:Ligands; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; D009355:Neomycin; D013095:Spermidine