Callipeltin A, a Cyclic Depsipeptide Inhibitor of the Cardiac Sodium–Calcium Exchanger and Positive Inotropic Agent

• Published in: Biochemical and biophysical research communications Vol. 279; no. 1; pp. 219 - 222
• Main Authors: Trevisi, L., Bova, S., Cargnelli, G., Danieli-Betto, D., Floreani, M., Germinario, E., D'Auria, M.V., Luciani, S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.12.2000
• Subjects: 3',5'-Cyclic-AMP Phosphodiesterases - drug effects; Animals; Calcium-Transporting ATPases - drug effects; Callipeltin A; cardiac Na+/Ca2+ exchanger; Cattle; Cyclic Nucleotide Phosphodiesterases, Type 3; Depsipeptides; guinea pig atria; Guinea Pigs; Myocardial Contraction - drug effects; Myocardium - metabolism; Peptides, Cyclic - metabolism; Peptides, Cyclic - pharmacology; positive inotropic effect; Sodium-Calcium Exchanger - antagonists & inhibitors; Sodium-Calcium Exchanger - metabolism; Sodium-Potassium-Exchanging ATPase - drug effects; guinea pig atria; Callipeltin A; cardiac Na+/Ca2+ exchanger; positive inotropic effect
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2000.3906

Callipeltin A, a cyclic depsipeptide from the New Caledonian Lithistida sponge Callipelta sp., is a macrocyclic lactone containing four amino acids in the L configuration, Ala, Leu, Thr (2 residues); one (Arg) in the D configuration; two N-methyl amino acids, N-MeAla and N-MeGln; a methoxy tyrosine, a 3,4-dimethyl-l-glutamine; and a 4-amino-7-guanidino-2,3 dihydroxypentanoic acid (AGDHE), formally derived from L-Arg. In cardiac sarcolemmal vesicles Callipeltin A induces a powerful (IC50 = 0.85 μM) and selective inhibition of the Na+/Ca2+ exchanger. In electrically driven guinea-pig atria, at concentrations ranging between 0.7 and 2.5 μM, Callipeltin A induces a positive inotropic effect, which at the highest concentrations is accompanied by a rise in resting tension. It is suggested that the positive inotropic effect is linked to the inhibition of the Na+/Ca2+ exchanger and that Callipeltin A may be an useful tool to study the role of the cardiac Na+/Ca2+ exchanger in physiological and pathological conditions.