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Neuropeptide W (NPW) is produced in neurons located in hypothalamus and brain stem, and its receptors are present in the hypothalamus, in particular in the paraventricular nucleus (PVN). Intracerebroventricular (ICV) administration of NPW activated, in a dose-related fashion, the hypothalamic-pituitary-adrenal axis, as determined by plasma corticosterone levels in conscious rats but, at those same doses, did not stimulate the release of oxytocin or vasopressin into the peripheral circulation or alter blood pressure or heart rate. The ability of ICV-administered NPW to stimulate the hypothalamic-pituitary-adrenal axis in conscious male rats was blocked by intravenous pretreatment with a corticotropin-releasing hormone antagonist. This suggested an action of NPW in the parvocellular division of the PVN. Indeed, in hypothaiamic slice preparations (whole cell patch recording), bath application of NPW depolarized and increased the spike frequency of the majority of electrophysiologically identified putative neuroendocrine PVN neurons. Effects on membrane potential were maintained in the presence of TTX, suggesting them to be direct postsynaptic actions on these neuroendocrine cells. Our data suggest that endogenous NPW, produced in brain, may play a physiologically relevant role in the neuroendocrine response to stress. corticotropin-releasing hormone; corticosterone

Orexinergic neurons originating in the perifornical, lateral hypothalamus project to numerous brain sites including neuroendocrine centers known to be important in the physiologic response to stress. Those projections suggest an action of endogenous orexin on adrenocorticotropin (ACTH) release, either by neuromodulatory effects in the paraventricular nucleus (PVN), or by neuroendocrine actions in the pituitary gland following release into the median eminence. We sought to determine if exogenously applied orexin A might act in the brain to alter ACTH release and to determine if a site of action in the hypothalamic paraventricular nucleus could be identified. Cerebroventricular administration of orexin A in conscious male rats resulted in a dose-related elevation in circulating ACTH levels. At 30 min post-infusion, ACTH levels were elevated 2.5-fold by the low dose of orexin A (0.3 nmol), 5.7-fold by the middle dose tested (1.0 nmol), and 7.5-fold by the highest dose tested (3.0 nmol). Pretreatment with a CRH-antagonist (i.v.) blocked the ability of i.c.v. administered orexin A to activate the hypothalamo-pituitary-adrenal (HPA) axis. Bath application of orexin A in hypothalamic slice preparations resulted in depolarizations (8.0±0.6 mV), accompanied by increases in spike frequency in identified magno- and parvocellular neurons in the PVN. Our data suggest a potential role for endogenous orexin in the hypothalamic regulation of stress hormone secretion. [Copyright &y& Elsevier]

Presents information on a study which examined the possibility that the hypocretin/orexins could alter stress hormone secretion by a direct pituitary action. Materials and methods; Results and discussion.