TY - JOUR
T1 - Spermine-induced negative inotropic effect in isolated rat heart, is mediated through the release of ATP
AU - Guevara-Balcázar, Gustavo
AU - Querejeta-Villagómez, Enrique
AU - Nuevo-Adalla, Oskar
AU - Orozco-Guillen, Alejandra
AU - Rubio-Gayosso, Ivan
AU - Hernández-Castillo, Jose R.
AU - Zamora-Garza, Miguel
AU - Ceballos-Reyes, Guillermo
N1 - Funding Information:
This work was supported by the Instituto Politécnico Nacional and CONACyT grants 31423-M and G34998-N. The authors thank Dr. M.J. Willard (M.J. Willard MD/FRCPC, Unit 1 Westam Laboratory, 150 Mctavish Avenue East, Brandon, Man., Canada. Tel.: +1-204-726-2003) for the grammar revision of manuscript.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - 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 (0.1-0.6mM) 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), H1 and H2 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 P2y 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.
AB - 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 (0.1-0.6mM) 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), H1 and H2 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 P2y 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.
KW - Heart
KW - Inotropism
KW - Polyamines
KW - Pressure
KW - Spermine
KW - Ventricular contraction force
UR - http://www.scopus.com/inward/record.url?scp=0038005559&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(03)00238-7
DO - 10.1016/S0006-2952(03)00238-7
M3 - Artículo
SN - 0006-2952
VL - 66
SP - 157
EP - 161
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 1
ER -