In vivo structure activity study supports the existence of heterogeneous neuropeptide Y receptors

The purpose of the present study was to examine relationships between structure and activity of the peptide for stimulating food intake and decreasing body temperature in rats. Various NPY fragments and structural analogs were administered intracerebroventricularly in several doses (2.5-160 micrograms) and their effects on feeding and body temperature evaluated and compared. Globally, results indicate that the C-terminal portion of the peptide is responsible for both central effects of NPY. However, the distributions of potencies of the various fragments and analogs for increasing food intake and decreasing body temperature were clearly different. The most salient difference was that deletion of the N-terminal residue Tyr1 of NPY resulted in a five-fold loss in the potency for decreasing rectal temperature, whereas NPY2-36 was relatively more potent than the native peptide to increase food intake in animals. These results suggest that the purported receptors mediating the effect of NPY on food intake are different than those responsible for the influence of the peptide on body temperature. The results of the present in vivo work are discussed in relation to those obtained in previous in vitro studies.