Analysis of NPY receptor subtypes in the human frontal cortex reveals abundant Y1 mRNA and binding sites.

ABSTRACT

Receptors for neuropeptide Y (NPY) are widely distributed throughout the mammalian brain. Using indirect labeling methods, the human brain was reported to contain predominantly the Y2 receptor subtype, whereas the rat brain contains a mixture of Y1 and Y2 receptor subtypes. To more accurately assess NPY receptors in the human brain, we used type Y1- and Y2-selective radioligands [125I] [Leu31,Pro34]PYY and [125I]PPY (3-36), respectively, to examine NPY receptors in the human frontal cortex. Contrary to an earlier report, abundant Y1 binding sites were found in homogenates of human frontal cortex. Moreover, saturation analysis showed similar densities of both Y1 (Kd = 433 +/- 36 pM, Bmax = 313 +/- 15 fmol/mg protein) and Y2 (Kd = 444 +/- 39 pM, Bmax = 458 +/- 22 fmol/mg protein) receptor subtypes in the human frontal cortex. Subsequently, Northern blot analysis revealed abundant expression of Y1 mRNA, with very low levels of Y2 mRNA, in cerebral cortex and in other areas of the human brain. These findings were confirmed by competitive RT-PCR in the human frontal cortex. Therefore, it appears that Y1 binding sites and mRNA are expressed abundantly in the human frontal cortex and, earlier findings, suggest that the human brain contains a mixture of Y1 and Y2 receptor subtypes.