Functional autoradiography of neuropeptide Y Y1 and Y2 receptor subtypes in rat brain using agonist stimulated [35S]GTPgammaS binding.
Neuropeptide Y, one of the most abundant brain peptides, has been found to modulate several important biological functions via a family of G-protein coupled receptors. To investigate the localization of functional NPY receptor subtypes in the rat brain, we performed agonist-induced [35S]GTPgammaS autoradiography. The Y1/Y4/Y5 agonist Leu(31), Pro(34)-NPY increased [35S]GTPgammaS binding in several brain areas with a regional distribution consistent with that produced when labeling adjacent sections with [125I]-Leu(31), Pro(34)-PYY. The Y1 selective antagonist BIBP3226 antagonized the Leu(31), Pro(34)-NPY stimulated increase in [35S]GTPgammaS binding in all areas examined. The Y2 agonist C2-NPY stimulated [35S]GTPgamma binding in numerous brain areas with a regional distribution similar to the binding observed with [125I]-PYY 3-36. No increase in [35S]GTPgammaS binding above basal was observed in any brain area evaluated using Y4 and Y5 selective agonists. This study demonstrates abundant Y1 and Y2 receptor activation in the rat brain, while evidence for functional Y4 and Y5 receptors was not observed.
Shaw
Janice L
JL
Neuroscience Research, Lilly Research Laboratories, Eli Lilly and Company, Mail Code 0510, Indianapolis, IN 46285, USA.
Gackenheimer
Susan L
SL
Gehlert
Donald R
DR
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D004027:Diencephalon / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D020540:Metencephalon / Q000378:metabolism; D009833:Olfactory Pathways / Q000378:metabolism; D010446:Peptide Fragments; D019894:Peptide YY / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D013687:Telencephalon / Q000378:metabolism
D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; D013462:Sulfur Radioisotopes; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; D019894:Peptide YY; C061785:peptide YY (3-36); D016244:Guanosine 5'-O-(3-Thiotriphosphate)