title: Spermine-induced negative inotropic effect in isolated rat heart, is mediated through the release of ATP.
abstract: Putrescine, spermidine and spermine are natural compounds found in up to millimolar concentrations in eukaryotic and prokaryotic cells. At physiologic pH, the polyamines are protonated (+2, +3 and +4 charges), their polycationic properties lead to the assumption that they could affect physiological systems by binding to anionic sites of the cellular membrane and/or by modulating ion channels. At the cardiovascular level, their effects are not completely understood. However, these compounds may be able to exert the induction of synthesis and release of cellular mediators. In an attempt to explore this possibility, we used the isolated and perfused rat heart, Langendorff, model in order to evaluate the inotropic effects of these polyamines, putrescine, spermidine and spermine. Dose-response curves (0.1-0.6 mM) for putrescine, spermidine and spermine were constructed; with the finding that spermine had the largest negative effect. The obtained effects were not blocked by nitric oxide synthesis inhibitors (L-NAME), H(1) and H(2) receptor antagonists (Brompheniramine and Cimetidine) or by Glibenclamide, an antagonist of ATP-sensitive K(+) channels. We found that spermine-induced and increased ATP concentration in cardiac effluents. Reactive Blue, a P(2y) purinoreceptor antagonist and Aminophylline, an unspecific adenosine receptor antagonist, blocked the spermine-induced effects. These results showed that ATP, at least in part, is responsible of the spermine cardiovascular effects. Adenosine was shown to also play an important role on those effects.
authors.affiliation: Laboratorio Multidisciplinario, Sección de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón S/N, col. Santo Tomas, México D.F. CP 11340, Mexico.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Guevara-Balcázar
authors.forename: Enrique
authors.initials: E
authors.lastname: Querejeta-Villagómez
authors.forename: Oskar
authors.initials: O
authors.lastname: Nuevo-Adalla
authors.forename: Alejandra
authors.initials: A
authors.lastname: Orozco-Guillen
authors.forename: Ivan
authors.initials: I
authors.lastname: Rubio-Gayosso
authors.forename: Jose R
authors.initials: JR
authors.lastname: Hernández-Castillo
authors.forename: Miguel
authors.initials: M
authors.lastname: Zamora-Garza
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ceballos-Reyes
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D011687:Purines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000494:pharmacology*
chemical_list: D011073:Polyamines; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D011687:Purines; D013096:Spermine; D000255:Adenosine Triphosphate