Nesfatin-1 evokes Ca2+ signaling in isolated vagal afferent neurons via Ca2+ influx through N-type channels

Nesfatin-1, processed from nucleobindin 2, is an anorexigenic peptide expressed in the brain and several peripheral tissues including the stomach and pancreas. Peripheral, as well as intracerebroventricular, administration of nesfatin-1 suppresses feeding behavior, though underlying mechanisms are unknown. In this study, we examined effects of nesfatin-1 on cytosolic Ca2+ concentration ([Ca2+](i)) in the neurons isolated from the vagal afferent nodose ganglion of mice. Nesfatin-1 at 10(-10)-10(-8) M increased [Ca2+](i), in the isolated neurons in a concentration-dependent manner, and at 10(-8) M it increased [Ca2+](i), in 33 out of 263 (12.5%) neurons. These responses were inhibited under Ca2+-free conditions and by N-type Ca2+ channel blocker, omega-conotoxin GVIA. All the nesfatin-1-responsive neurons also exhibited [Ca2+](i) responses to capsaicin and cholecystokinin-8. These results provide direct evidence that nesfatin-1 activates vagal afferent neurons by stimulating Ca2+ influx through N-type channels, demonstrating the machinery through which peripheral nesfatin-1 can convey signals to the brain. (C) 2009 Elsevier Inc. All rights reserved.