Structure-activity analysis of the motor effects of neuropeptide Y.

The purpose of the present study was to examine structure-activity relationships for three known motor effects of neuropeptide Y (NPY): decreased spontaneous activity, enhancement of muscle tone, and catalepsy. Various NPY fragments and structural analogues were synthesized and administered intracerebroventricularly in several doses (2.5-160 micrograms); their effects on these three motor variables were evaluated and compared. Globally, results indicate that the C-terminal portion of the peptide is responsible for the three motor effects of NPY. However, the distributions of potencies of the various fragments and analogues for each effect were clearly different, suggesting that the putative receptors mediating each motor effect are pharmacologically different. The findings of the present work are discussed in relation to those obtained in previous structure-activity studies.

Neurobehavioral profile of neuropeptide Y.

In order to better delineate the profile of central actions of neuropeptide Y (NPY), the effects of intracerebroventricular administration of several doses (2.5-20 micrograms) of the peptide on spontaneous activity, muscular tone, body temperature, food intake, nociception and cataleptic manifestations were examined in rats. Results indicate that, starting at 5 micrograms. NPY significantly decreased motor activity of animals in a dose-related fashion. NPY also significantly lowered body temperature of animals. The hypothermic effect was obtained following injections of 10.0 and 20.0 micrograms of the peptide. Administration of the same two doses of NPY resulted in significant increases in food intake, muscular tone and induced a significant catalepsy in animals. On the other hand, nociceptive response times of animals in the hot plate test were not affected by any of the NPY doses tested. Together, these results indicate that the profile of NPY's neurobehavioral actions is more complex than previously reported and suggest that the peptide might be implicated functionally in a variety of neurophysiological processes.

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.