Nesfatin-1 as a new positive inotrope in the goldfish (Carassius auratus) heart

作者：Mazza R; Gattuso A; Filice M; Cantafio P; Cerra M C; Angelone T; Imbrogno S^*

来源：General and Comparative Endocrinology, 2015, 224: 160-167.

DOI：10.1016/j.ygcen.2015.08.003

• Nesfatin-1
• Cardiac performance
• Inotropism
• Signal transduction
• cAMP

The hypothalamic neuropeptide Nesfatin-1 is present in both mammals and teleosts in which it elicits anorexigenic effects. In mammals, Nesfatin-1 acts on the heart by inducing negative inotropism and lusitropism, and cardioprotection against ischemic damages. We evaluated whether in teleosts, Nesfatin-1 also influences cardiac performance. In the goldfish (Carassius auratus), mature, fully processed Nesfatin-1 was detected in brain, gills, intestine and skeletal muscle, but not in the cardiac ventricle. However, on the isolated and perfused working goldfish heart, exogenous Nesfatin:1 induced a positive inotropic effect, revealed by a dose-dependent increase of stroke volume (SV) and stroke work (SW). Positive inotropism was abolished by inhibition of adenylate cyclase (AC; MDL123330A) and cAMP-dependent kinase (PKA; KT5720), suggesting a cAMP/PKA-mediated pathway. This was confirmed by the increased cAMP concentrations revealed by ELISA on Nesfatin-1 -treated hearts. Perfusion with Diltiazem, Thapsigargin and PD98059 showed the involvement of L-type calcium channels, SERCA2a pumps and ERK1/2, respectively. The role of ERK1/2 and phospholamban in Nesfatin-1-induced cardiostimulation was supported by Western blotting analysis.
In conclusion, this is the first report showing that in teleosts, Nesfatin-1 potentiates mechanical cardiac performance, strongly supporting the evolutionary importance of the peptide in the control of the cardiac function of vertebrates.

• 出版日期2015-12-1