Digitalis-like and vasoconstrictor effects of endogenous digoxin-like factor(s) from the venom of Bufo marinus toad.
Digitalis glycoside-like properties of the Bufo marinus toad crude venom and one of its constituents, bufalin, were studied in various assay systems. In concentrations 0.3-30 micrograms/ml crude venom increased the contractility of isolated electrically driven rat atria, constricted rat aortic rings, inhibited ouabain-sensitive Na+,K(+)-ATPase in rat erythrocytes and the Na+,K(+)-pump in rat aorta, and cross-reacted with antidigoxin antibody from the dissociation enhanced lanthanide fluoroimmunoassay (DELFIA). These effects were unaffected by adrenoceptor blockers and the 5-HT antagonist, deseril, but were blocked by antidigoxin antibody. Bufalin (10-30 microM) increased myocardial contractility and inhibited Na+,K(+)-ATPase in rat erythrocytes similarly to crude Bufo marinus venom. In rat aorta bufalin showed weak and delayed vasoconstrictor activity which was antagonized by 2 microM phentolamine, and had a biphasic effect on the Na+,K(+)-pump; 0.5-1.0 microM bufalin stimulated the pump, while higher concentrations inhibited its activity. Although the effects of bufalin were blocked by antidigoxin antibody, bufalin showed very low digoxin-like immunoreactivity in the DELFIA. These observations suggest that, in addition to bufalin, Bufo marinus venom contains at least one more digitalis-like steroid with significant intrinsic vasoconstrictor activity which, unlike bufalin, constricts the blood vessels acting directly via inhibition of the sodium pump in the vascular smooth muscle membrane.
Division of Cardiology, I.I. Dzhanelidze First Aid (Emergency Medicine), Research Institute, St. Petersburg, Russian Federation.
A Y
AY
Bagrov
N I
NI
Roukoyatkina
O V
OV
Fedorova
A G
AG
Pinaev
M V
MV
Ukhanova
D000664:Amphibian Venoms / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects; D001798:Blood Proteins / Q000276:immunology / Q000494:pharmacology*; D002018:Bufanolides / Q000494:pharmacology; D002024:Bufo marinus; D002298:Cardenolides; D004071:Digitalis Glycosides / Q000494:pharmacology*; D004077:Digoxin / Q000276:immunology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D007074:Immunoglobulin G / Q000276:immunology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D010306:Parotid Gland / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins; D015222:Sodium Channels / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D000664:Amphibian Venoms; D001798:Blood Proteins; D002018:Bufanolides; D002298:Cardenolides; D004071:Digitalis Glycosides; D007074:Immunoglobulin G; D012503:Saponins; D015222:Sodium Channels; C034504:digoxin-like factors; D010042:Ouabain; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase; C022777:bufalin