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

Rosa Mazza, Cinzia Mannarino, Sandra Imbrogno, Sandra Francesca Barbieri, Cristina Adamo, Tommaso Angelone, Angelo Corti, Bruno Tota

Research output: Contribution to journalArticle

Abstract

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: 1 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.

Original languageEnglish
Pages (from-to)145-151
Number of pages7
JournalRegulatory Peptides
Volume138
Issue number2-3
DOIs
Publication statusPublished - Feb 1 2007

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Keywords

  • BDM
  • Cytochalasin-D
  • Heart preparations
  • Vasostatins
  • W7
  • Wortmannin

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Neuroscience(all)

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