CHARACTERIZATION OF THE NEUROPEPTIDE Y5 RECEPTOR IN THE HUMAN HYPOTHALAMUS - A LACK OF CORRELATION BETWEEN Y5 MESSENGER-RNA LEVELS AND BINDING-SITES

Neuropeptide Y (NPY) is a 36-amino-acid peptide that appears to play a central role in the control of feeding behavior. Recently, a cDNA enc oding a novel NPY receptor subtype (Y5) was cloned from the rat and hu man hypothalamus, and shown to have a pharmacology consistent with NPY -induced feeding. We have subsequently cloned this cDNA from human hyp othalamus and stably expressed it in CHO cells. Consistent with earlie r reports, hY5 has a high affinity for NPY, [Leu(31),Pro(34)]NPY and N PY(3-36), but low affinity for larger C-terminal deletions of NPY and BIBP3226. High levels of hY5 mRNA were found in the human testis, brai n, spleen and pancreas, with lower levels in several other tissues. In the human brain, hY5 mRNA levels were typically higher than hY2, but lower in comparison to hY1 receptor mRNA. To quantify the relative amo unts of hY1, hY2 and hY5 mRNA in the human hypothalamus, we employed c ompetitive RT-PCR. Interestingly, the relative amount of hY5 mRNA was substantially higher than either hY1 or hY2. However, pharmacological characterization of NPY binding sites in human hypothalamus membranes revealed predominantly the hY2 subtype. These data establish that whil e hY5 mRNA levels are very high in the human hypothalamus, conventiona l radioligand binding techniques do not detect hY5-like binding site. Whether hY5-like binding sites exist in the other human tissues that e xpress hY5 mRNA (and what function hY5 has in those tissues) awaits fu ture investigation. (C) 1998 Elsevier Science B.V. All rights reserved .