HIGH-AFFINITY NEUROPEPTIDE-Y RECEPTOR ANTAGONISTS

Neuropeptide Y (NPY) is one of the most abundant peptide transmitters in the mammalian brain. In the periphery it is costored and coreleased with norepinephrine from sympathetic nerve terminals. However, the ph ysiological functions of this peptide remain unclear because of the ab sence of specific high-affinity receptor antagonists. Three potent NPY receptor antagonists were synthesized and tested for their biological activity in in vitro, ex vivo, and in vivo functional assays. We desc ribe here the effects of these antagonists inhibiting specific radiola beled NPY binding at Y1 and Y2 receptors and antagonizing the effects of NPY in human erythroleukmia cell intracellular calcium mobilization , perfusion pressure in the isolated rat kidney, and mean arterial blo od pressure in anesthetized rats.