Neuropeptide W as a stress mediator in the hypothalamus.

Neuropeptide W (NPW) was isolated and found to be an endogenous peptide ligand for the orphan receptors GPR7 and GPR8. Centrally administered NPW caused a dose-dependent increase in corticosterone levels in rats. This observation indicates that NPW may play an important role in the hypothalamic organization of the endocrine response to stress. We examined the effects of immobilization stress and cold exposure on NPW-containing neurons in the hypothalamus of the rat, using dual immunostaining for NPW and Fos. In addition, to analyze the function of NPW, we studied the effect of intracerebroventricular (icv) NPW administration on Fos protein accumulation in the brain. Double immunohistochemistry for NPW and Fos showed that the percentage of Fos expression in the NPW-immunoreactive cells of the perifornical nucleus was significantly increased by immobilization stress compared with that in nonstressed rats. Similarly, the results indicated that cold exposure activates NPW-immunoreactive neurons in the perifornical nucleus. An icv administration of NPW resulted in significant Fos expression in the paraventricular nucleus, as compared with saline-infused controls. These results suggest that NPW is related to stress-responsive signal transduction, and that NPW may modulate the hypothalamus-pituitary-adrenal axis.