Differential regulation of neuropeptide Y receptors in the brains of NPY knock-out mice

To study the effect of NPY deletion on the regulation of its receptors in t he NPY knockout (NPY KO) mice, the expression and binding of NPY receptors were investigated by in situ hybridization and receptor autoradiography usi ng I-125-[Leu(31),Pro(34)]PYY and I-125-PYY3-36 as radioligands. A 6-fold i ncrease in Y2 receptor mRNA was observed in the CA1 region of the hippocamp us in NPY KO mice, but a significant change could not be detected for Y1, Y 4, Y5 and y6 receptors. Receptor binding reveals a 60-400% increase of Y2 r eceptor binding in multiple brain areas. A similar increase in Y1 receptor binding was seen only in the hypothalamus. These results demonstrate the NP Y receptor expression is altered in mice deficient for its natural ligand. (C) 2001 Elsevier Science Inc. All rights reserved.