Crucial role of cytoskeleton reorganization in the negative inotropic effect of chromogranin A-derived peptides in eel and frog hearts.
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.
Mazza
Rosa
R
Department of Cell Biology, University of Calabria, 87030 Arcavacata di Rende (CS), Italy. r.mazza@unical.it
Mannarino
Cinzia
C
Imbrogno
Sandra
S
Barbieri
Sandra Francesca
SF
Adamo
Cristina
C
Angelone
Tommaso
T
Corti
Angelo
A
Tota
Bruno
B
D000704:Analysis of Variance; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001001:Anura; D037282:Calreticulin / Q000494:pharmacology; D053379:Chromogranin A / Q000737:chemistry*; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D003931:Diacetyl / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004524:Eels; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D000077191:Wortmannin
D000730:Androstadienes; D037282:Calreticulin; D053379:Chromogranin A; D010446:Peptide Fragments; D010455:Peptides; C121986:vasostatin; C004717:diacetylmonoxime; D015638:Cytochalasin D; D010741:Phospholipases A; D003931:Diacetyl; D000077191:Wortmannin