Crucial role of cytoskeleton reorganization in the negative inotropic effect of chromogranin A-derived peptides in eel and frog hearts

• Published in: Regulatory Peptides
• Main Authors: Mazza R, Mannarino C, Imbrogno S, Barbieri SF, Adamo C, Angelone T, Tota B., CORTI , ANGELO
• Other Authors: Mazza, R, Mannarino, C, Imbrogno, S, Barbieri, Sf, Adamo, C, Angelone, T, Corti, Angelo, Tota, B.
• Format: Article in Journal/Newspaper
• Language: unknown
• Published: 2007
• Subjects: Anguilla anguilla
• Online Access: https://hdl.handle.net/20.500.11768/2914; https://doi.org/10.1016/j.regpep.2006.09.002

Vasostatins (VSs), i.e. the main biologically active peptides generated by the proteolytic processing of chromogranin A (CGA) N-terminus, exert negative inotropism in vertebrate hearts. Here, using isolated working eel (Anguilla anguilla) and frog (Rana esculenta) heart preparations, we have studied the role of the cytoskeleton in the VSs-mediated inotropic response. In both eel and frog hearts, VSs-mediated-negative inotropy was abolished by treatment with inhibitors of cytoskeleton reorganization, such as cytochalasin-D (eel: 10 nM; frog: 1 nM), an inhibitor of actin polymerisation, wortmannin (0.01 nM), an inhibitor of PI3-kinase (PI3-K)/protein kinase B (Akt) signal-transduction cascade, butanedione 2-monoxime (BDM) (eel: 100 nM; frog: 10 nM), an antagonist of myosin ATPase, and N-(6-aminohexil)-5-chloro-1-naphthalenesulfonamide (W7) (eel: 100 nM; frog: I nM), a calcium-calmodulin antagonist. These results demonstrate that changes in cytoskeletal dynamics play a crucial role in the negative inotropic influence of VSs on eel and frog hearts. (c) 2006 Elsevier B.V. All rights reserved.