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 originating from plants (phyto-bufadienolides) on the Na+/K+ pump current (Ip) in cardiac (rat and guinea pig) and dorsal root ganglion cells (guinea pig), and on Ca2+ currents in cardiomyocytes (guinea pig). All bufadienolides tested (non-cumulative drugs: thesiuside, tyledoside C; lanceotoxin B and tyledoside F for the neurotoxic group) were potent blockers of Ip at concentrations in the micro- and submicromolar range. K0.5 values for Ip inhibition in dorsal root ganglion neurones were slightly lower compared to cardiomyocytes, but the order of potency was similar in both cell types. Both classes of bufadienolides were equipotent in suppressing Ip, generated by high- and low-affinity pump isoforms. Phenomena related to pump inhibition, as hypercontracture and increase 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 affinity.
Van der Walt
J J
JJ
Department of Physiology, Potchefstroom University for CHE, South Africa.
Van Rooyen
J M
JM
Kellerman
T S
TS
Carmeliet
E E
EE
Verdonck
F
F
D000818:Animals; D002018:Bufanolides / Q000378:metabolism / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010944:Plants; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D002018:Bufanolides; D015220:Calcium Channels; D000254:Sodium-Potassium-Exchanging ATPase