NEUROSPECIFICITY OF PHYTO-BUFADIENOLIDES IS NOT RELATED TO DIFFERENCES IN NA+ K+ PUMP INHIBITION/

The aim of the present study was to investigate the effects of neuro- (cumulative) and cardiotoxic (non-cumulative) bufadienolides originati ng from plants (phyto-bufadienolides) on the Na+/K+ pump current (I-p) in cardiac (rat and guinea pig) and dorsal root ganglion cells (guine a pig), and on Ca2+ currents in cardiomyocytes (guinea pig). All bufad ienolides tested (non-cumulative drugs: thesiuside, tyledoside C; lanc eotoxin B and tyledoside F for the neurotoxic group) were potent block ers of I-p at concentrations in the micro- and submicromolar range. K- 0.5 values for I-p inhibition in dorsal root ganglion neurones were sl ightly lower compared to cardiomyocytes, but the order of potency was similar in both cell types. Both classes of bufadienolides were equipo tent in suppressing I-p, generated by high and low-affinity pump isofo rms. Phenomena related to pump inhibition, as hypercontracture and inc rease in T-type Ca2+ current in cardiomyocytes, were influenced to the same extent. Therefore, from these results, neurospecificity of some bufadienolides could not be explained by differences in Na+/K+ pump af finity. (C) 1997 Elsevier Science B.V.