Lithium inhibits internalization and endosomal processing of both neuropeptide Y (NPY) Y1 and transferrin receptors

Low concentrations of Li+ reduce the rate of internalization of neuropeptide Y (NPY) Y1 receptors [M.S. Parker, S.L. Parker, J.K. Kane, Internalization of neuropeptide Y Y1 and Y5 and of pancreatic polypeptide Y4 receptors is inhibited by lithium in preference to sodium and potassium ions, Regul. Pept., 118 (2004) 67-74]. This Li+-induced decrease in Y1 receptor internalization could be alleviated by Y1 receptor agonists. As shown by fractionation on Percoll gradients, lithium treatment induces a concentration-related decrease of intermediate and higher endosomal densities that contain the internalized Y1 ligand-receptor complex. This indicates an inhibition of endosome processing and maturation. Internalization of human transferrin shows [Li+] sensitivity similar to that of the Y1 receptor, and a similar Li+-induced decrease in endosomal processing. Lithium treatment thus decreases activity of the endosome system shared in the recycling endocytosis of the Y1 and transferrin receptors.