SUBTYPES OF RECEPTORS FOR NEUROPEPTIDE-Y - IMPLICATIONS FOR THE TARGETING OF THERAPEUTICS

Neuropeptide Y is a 36 amino acid peptide that was originally discover ed in extracts of porcine brain. The peptide has a broad distribution in the central or peripheral nervous system. Receptors for this peptid e were originally subdivided into postsynaptic Y-1 receptors and presy naptic Y-2 receptors. The Y-1 receptor has recently been cloned and ap pears to mediate several effects of NPY including vasoconstriction and an anxiolytic effect in animal models of anxiety. The Y-2 receptor in hibits the release of neurotransmitters in the CNS by the inhibition o f the mobilization of intracellular calcium. Additional receptors have been proposed including a Y-3 receptor that recognizes NPY but not th e related endocrine peptide, PYY. The functional importance of these n ewer receptors remains to be established. The absence of useful antago nists has made the study of NPY a challenge for investigators in the f ield. The potential utility of such molecules is discussed.