Nesfatin-1 activates cardiac vagal neurons of nucleus ambiguus and elicits bradycardia in conscious rats.

Authors

G Cristina Brailoiu, Department of Pharmaceutical Sciences, Thomas Jefferson University, Jefferson School of PharmacyFollow
Elena Deliu, Department of Pharmacology, Center for Translational Medicine, Temple University School of MedicineFollow
Andrei A Tica, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine
Joseph E Rabinowitz, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine; Center for Translational Medicine, Temple University School of MedicineFollow
Douglas G Tilley, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine; Center for Translational Medicine, Temple University School of MedicineFollow
Khalid Benamar, Center for Substance Abuse Research, Temple University School of Medicine
Walter J Koch, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine; Center for Translational Medicine, Temple University School of MedicineFollow
Eugen Brailoiu, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine; Center for Translational Medicine, Temple University School of MedicineFollow

Document Type

Article

Publication Date

9-1-2013

Comments

This article has been peer reviewed. It was published in: Journal of Neurochemistry.

Volume 126, Issue 6, September 2013, Pages 739-748.

The published version is available at DOI: 10.1111/jnc.12355

Copyright © 2013 International Society for Neurochemistry.

Abstract

Nesfatin-1, a peptide whose receptor is yet to be identified, has been involved in the modulation of feeding, stress, and metabolic responses. More recently, increasing evidence supports a modulatory role for nesfatin-1 in autonomic and cardiovascular activity. This study was undertaken to test if the expression of nesfatin-1 in the nucleus ambiguus, a key site for parasympathetic cardiac control, may be correlated with a functional role. As we have previously demonstrated that nesfatin-1 elicits Ca²⁺ signaling in hypothalamic neurons, we first assessed the effect of this peptide on cytosolic Ca²⁺ in cardiac pre-ganglionic neurons of nucleus ambiguus. We provide evidence that nesfatin-1 increases cytosolic Ca²⁺ concentration via a Gi/o-coupled mechanism. The nesfatin-1-induced Ca²⁺ rise is critically dependent on Ca²⁺ influx via P/Q-type voltage-activated Ca²⁺ channels. Repeated administration of nesfatin-1 leads to tachyphylaxis. Furthermore, nesfatin-1 produces a dose-dependent depolarization of cardiac vagal neurons via a Gi/o-coupled mechanism. In vivo studies, using telemetric and tail-cuff monitoring of heart rate and blood pressure, indicate that microinjection of nesfatin-1 into the nucleus ambiguus produces bradycardia not accompanied by a change in blood pressure in conscious rats. Taken together, our results identify for the first time that nesfatin-1 decreases heart rate by activating cardiac vagal neurons of nucleus ambiguus. Our results indicate that nesfatin-1, one of the most potent feeding peptides, increases cytosolic Ca²⁺ by promoting Ca²⁺ influx via P/Q channels and depolarizes nucleus ambiguus neurons; both effects are Gi/o-mediated. In vivo studies indicate that microinjection of nesfatin-1 into nucleus ambiguus produces bradycardia in conscious rats. This is the first report that nesfatin-1 increases the parasympathetic cardiac tone.

Recommended Citation

Brailoiu, G Cristina; Deliu, Elena; Tica, Andrei A; Rabinowitz, Joseph E; Tilley, Douglas G; Benamar, Khalid; Koch, Walter J; and Brailoiu, Eugen, "Nesfatin-1 activates cardiac vagal neurons of nucleus ambiguus and elicits bradycardia in conscious rats." (2013). Center for Translational Medicine Faculty Papers. Paper 34.
https://jdc.jefferson.edu/transmedfp/34

PubMed ID

23795642