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.
Bagrov
A Y
AY
Division of Cardiology, I.I. Dzhanelidze First Aid (Emergency Medicine), Research Institute, St. Petersburg, Russian Federation.
Roukoyatkina
N I
NI
Fedorova
O V
OV
Pinaev
A G
AG
Ukhanova
M V
MV
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