Neuropeptide Y1 subtype pharmacology of a recombinantly expressed neuropeptide receptor.

Neuropeptide Y (NPY) is an important central and peripheral modulator of neural and endocrine functions. This neuropeptide interacts with at least two pharmacologically distinct receptors, termed Y1 and Y2. At Y1 receptors, the NPY analog Leu31,Pro34] NPY, but not the carboxyl-terminal fragment NPY-(18-36), displaces radiolabeled NPY and the sequence-related peptide YY, whereas Y2 receptors exhibit the opposite selectivity. We have used cultured mammalian 293 cells for the high level transient expression of a previously cloned putative neuropeptide receptor of rat brain. We report that this receptor displays the ligand binding properties and selectivity of a Y1 receptor, with a single high affinity site for 125I-NPY (Kd, 0.7 +/- 0.2 nM). The functionality of the recombinantly expressed receptor was demonstrated by an inhibition of adenylyl cyclase and a concomitant mobilization of intracellular Ca2+.