Comparison between effects of AMP579 and adenosine on Na+/Ca2+ exchanger in isolated rat ventricular myocytes / 中国药理学与毒理学杂志

ABSTRACT

AIMTo elucidate possible mechanisms underlying the differences between 1S-[1a,2b,3b,4a(S*)]-4-[7-[[1-(3-chloro-2-thienyl)methylpropyl]propyl-amino]-3H-imidazo[4,5-b]pyridyl-3-yl]-N-ethyl-2,3-dihydroxycyclopentane carboxamide (AMP- 579) and adenosine in pharmacological and clinical effects. METHODSNa+/Ca2+ exchange current was recorded by patch-clamp technique in whole-cell configuration. RESULTSAMP579 significantly enhanced both outward and inward Na+/Ca2+ exchange currents in a concentration dependent manner. Neither infusion of an adenosine A1 receptor antagonist PD116948 30 μmol*L-1 or an adenosine A2 receptor antagonist DMPX 10 μmol*L-1 nor a protein kinase A special blocker KT 5720 0.2 μmol*L-1 or a protein kinase C special blocker GF 109203X 0.4 μmol*L-1 had effect on Na+/Ca2+exchange current increased by AMP579, suggesting that AMP579 possess a direct activating effect on Na+/Ca2+ exchange current. CONCLUSIONAMP579 possibly possesses a direct activating effect on Na+/Ca2+ exchange current.