Functional autoradiography of neuropeptide Y Y1 and Y2 receptor subtypes in rat brain using agonist stimulated [35S]GTPγS 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]GTPγS autoradiography. The Y1/Y4/Y5 agonist Leu31, Pro34-NPY increased [35S]GTPγS binding in several brain areas with a regional distribution consistent with that produced when labeling adjacent sections with [125I]-Leu31, Pro34-PYY. The Y1 selective antagonist BIBP3226 antagonized the Leu31, Pro34-NPY stimulated increase in [35S]GTPγS binding in all areas examined. The Y2 agonist C2-NPY stimulated [35S]GTPγ binding in numerous brain areas with a regional distribution similar to the binding observed with [125I]-PYY 3-36. No increase in [35S]GTPγS 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. [Copyright &y& Elsevier]