NEUROPEPTIDE-Y RECEPTOR SUBTYPES

Neuropeptide Y (NPY) is an amidated 36-amino acid peptide with a wide distribution in the central and peripheral nervous system. It can evoke numerous physiological responses by activating specific receptors. Studies using NPY analogs in various model systems and cell types demonstrate different orders of ligand potency and receptor binding affinity. These studies suggest the existence of multiple subtypes of NPY receptors. NPY has been described to bind to at least three different receptors, Y-1, Y-2 and Y-3. NPY has also been shown to interact with sigma receptor in vivo and in vitro. There are indications that more subtypes might exist. Ligand binding studies reveal that Y-1, Y-2 and Y-3 receptors are all G-protein coupled. It is not yet confirmed whether the sigma receptor that interacts with NPY is G-protein coupled. Some studies show that NPY receptors may interact with other classical receptors, including alpha- and beta-adrenoceptors and cholinergic receptors. In the case of alpha- and beta-adrenoceptors, the receptor-receptor interaction is possibly via a pertussis toxin-sensitive G-protein. NPY receptors are coupled to various signal transduction mechanisms including inhibition of adenylate cyclase, and stimulation or inhibition of increases in intracellular Ca2+. Specific links between individual NPY receptor subtype and a particular signal transduction pathway are not established.