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 Ca(2+) concentration ([Ca(2+)](i)) in the neurons isolated from the vagal afferent nodose ganglion of mice. Nesfatin-1 at 10(-10)-10(-8)M increased [Ca(2+)](i) in the isolated neurons in a concentration-dependent manner, and at 10(-8)M it increased [Ca(2+)](i) in 33 out of 263 (12.5%) neurons. These responses were inhibited under Ca(2+)-free conditions and by N-type Ca(2+) channel blocker, omega-conotoxin GVIA. All the nesfatin-1-responsive neurons also exhibited [Ca(2+)](i) responses to capsaicin and cholecystokinin-8. These results provide direct evidence that nesfatin-1 activates vagal afferent neurons by stimulating Ca(2+) influx through N-type channels, demonstrating the machinery through which peripheral nesfatin-1 can convey signals to the brain.
Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 320-0498, Japan. ysk-iwasaki@jichi.ac.jp
Yusaku
Y
Iwasaki
Hajime
H
Nakabayashi
Masafumi
M
Kakei
Hiroyuki
H
Shimizu
Masatomo
M
Mori
Toshihiko
T
Yada
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000080866:Nucleobindins; D012844:Sincalide / Q000494:pharmacology; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D001067:Appetite Depressants; D020864:Calcium Channels, N-Type; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; D000080866:Nucleobindins; D012844:Sincalide; D002211:Capsaicin; D002118:Calcium