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 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 (IC(50) = 0.85 microM) and selective inhibition of the Na(+)/Ca(2+) exchanger. In electrically driven guinea-pig atria, at concentrations ranging between 0.7 and 2.5 microM, 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(+)/Ca(2+) exchanger and that Callipeltin A may be an useful tool to study the role of the cardiac Na(+)/Ca(2+) exchanger in physiological and pathological conditions.
Trevisi
L
L
Department of Pharmacology and Anesthesiology, University of Padova, Padua, Italy.
Bova
S
S
Cargnelli
G
G
Danieli-Betto
D
D
Floreani
M
M
Germinario
E
E
D'Auria
M V
MV
Luciani
S
S
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000187:drug effects; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000187:drug effects; D002417:Cattle; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D047630:Depsipeptides; D006168:Guinea Pigs; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects
D047630:Depsipeptides; D010456:Peptides, Cyclic; D019831:Sodium-Calcium Exchanger; C418139:callipeltin A; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase