title: Callipeltin A: sodium ionophore effect and tension development in vascular smooth muscle.
abstract: Callipeltin A is a cyclic depsidecapeptide isolated from the marine sponges Callipelta sp. and Latrunculia sp. that has been previously shown to increase the force of contraction of guinea-pig atria through the inhibition of Na+/Ca2+ exchanger (NCX). We investigated the effect of callipeltin A on guinea-pig aortic rings contracted by procedures that activate NCX in "calcium entry mode". Callipeltin A did not inhibit these contractions. Resting aorta responded to callipeltin A with a remarkable contraction that was concentration-dependent (EC50 0.44microM). This contraction was not inhibited by the calcium channel blocker verapamil and was not mediated by the activation of alpha-adrenergic or endothelin-1 receptors. Pre-incubation of aortic rings with 0.5mM amiloride, an inhibitor of NCX, completely prevented callipeltin A-induced contraction. Furthermore, callipeltin A (EC50 0.51microM) increased Na+ efflux of Na-loaded erythrocytes. 1H and 13C NMR resonances of callipeltin A revealed small but significant changes in the titration with K+ and Na+ salts. It is suggested that the effect of callipeltin A on cardiac and vascular preparations is linked to a Na-ionophore action.
authors.affiliation: Department of Pharmacology and Anaesthesiology, University of Padua, Largo E. Meneghetti 2, 35131 Padua, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Trevisi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Cargnelli
authors.forename: Giulio
authors.initials: G
authors.lastname: Ceolotto
authors.forename: Italia
authors.initials: I
authors.lastname: Papparella
authors.forename: Andrea
authors.initials: A
authors.lastname: Semplicini
authors.forename: Angela
authors.initials: A
authors.lastname: Zampella
authors.forename: Maria Valeria
authors.initials: MV
authors.lastname: D'Auria
authors.forename: Sisto
authors.initials: S
authors.lastname: Luciani
mesh_terms: D000818:Animals; D001011:Aorta; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D047630:Depsipeptides; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007476:Ionophores / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D047630:Depsipeptides; D007476:Ionophores; D010456:Peptides, Cyclic; C418139:callipeltin A; D012964:Sodium; D002118:Calcium