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

Callipeltin A, a cyclic depsipeptide from the New Caledonian Lithistida sponge Callipelta sp., is a macrocyclic lactone contg. four amino acids in the L configuration, Ala, Leu, Thr (2 residues); one (Arg) in the D configuration; two N-Me 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 elec. driven guinea-pig atria, at concns. ranging between 0.7 and 2.5 μM, Callipeltin A induces a pos. inotropic effect, which at the highest concns. is accompanied by a rise in resting tension. It is suggested that the pos. 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 physiol. and pathol. conditions