Paraventricular nucleus nesfatin-1 neurons are regulated by pituitary adenylate cyclase-activating polypeptide (PACAP)

Nesfatin-1 is a neuropeptide localized in hypothalamic paraventricular nucleus (PVN). Previously, we have reported the mechanism of feeding suppression by nesfatin-1, and also reported the ability of nesfatin-1 in regulating stress response and the circadian feeding pattern. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide also related to the stress response, feeding, and regulation of cardiovascular and autonomic nervous systems. The neurons with receptors for PACAP are distributed in PVN. However, there are no reports showing the direct effect of PACAP on nesfatin-1 neurons. In order to explore the direct effect of PACAP on PVN nesfatin-1 neuron, we have measured the cytosolic free calcium ([Ca2+](i)) using fura-2 microfluorometry in single neurons isolated from PVN of adult rats, followed by immunocytochemical identification of nesfatin-1 neurons. PACAP at 10(-15) M to 10(-9) M increased [Ca2+](i) in dose dependent manner. PAC1 and VPAC2 receptor agonists also increased [Ca2+](i). Sixteen out of 40 neurons (40%) in PVN responded to 10(-9) M PACAP, and 12 out of 16 neurons (75%) which responded to 10(-9) M PACAP were found to be nesfatin-1 neurons. In this paper we show that PACAP directly activates nesfatin-1 neurons in PVN. The data suggest that nesfatin-1 controls feeding, stress response or autonomic response under PACAP regulation. (C) 2013 Elsevier Ireland Ltd. All rights reserved.