Subtypes of receptors for neuropeptide Y: implications for the targeting of therapeutics

Neuropeptide Y is a 36 amino acid peptide that was originally discovered in extracts of porcine brain. The peptide has a broad distribution in the central or peripheral nervous system. Receptors for this peptide were originally subdivided into postsynaptic Y-1 receptors and presynaptic Y-2 receptors. The Y-1 receptor has recently been cloned and appears to mediate several effects of NPY including vasoconstriction and an anxiolytic effect in animal models of anxiety. The Y-2 receptor inhibits the release of neurotransmitters in the CNS by the inhibition of the mobilization of intracellular calcium. Additional receptors have been proposed including a Y-3 receptor that recognizes NPY but not the related endocrine peptide, PYY. The functional importance of these newer receptors remains to be established. The absence of useful antagonists has made the study of NPY a challenge for investigators in the field. The potential utility of such molecules is discussed.