Activities of novel polyhydroxylated cardiotonic steroids purified from nuchal glands of the snake, Rhabdophis tigrinus

Abstract

Seven novel polyhydroxylated steroids were isolated from the nucho-dorsal glands of the snake, Rhabdophis tigrinus. Biological activities of these steroids in inhibiting (Na+ + K+)ATPase and in producing positive inotropic action were examined in comparison with those of ouabain and gamabufotalin. Gamabufotalin was approximately 10 times more potent than ouabain in inhibiting (Na+ + K+)ATPase. Two compounds, compounds III and XIII, of the seven, produced nearly equipotent enzyme inhibitory activity to ouabain. The activity of the remaining five was relatively low among the compounds tested. All compounds exhibited more or less positive inotropic action in the papillary muscle preparations. The ranking order of the potency was: gamabufotalin greater than ouabain and compound IV greater than compound III and XIII greater than compound I, II, XII and XIV.

Maternal provisioning of sequestered defensive steroids by the Asian snake Rhabdophis tigrinus

“…Regardless of the reason for the pattern, it may be beneficial to hatchling R. tigrinus to have gamabufotalin as their dominant bufadienolide. This compound is approximately 10 times more effective at inhibiting the sodium-potassium pump in canine kidney than ouabain (Azuma et al 1986), and thus may be more effective as an antipredator compound than other bufadienolides. However, the physiological activities of most of the other bufadienolides remain to be determined.…”

Natural products from the integument of nonavian reptiles

“…103 In vitro toxicity studies using mammalian kidney and heart preparations demonstrated that bufadienolides in the secretions inhibit (Na + + K + ) ATPase and are positively inotropic, 104 which are typical properties of these compounds.…”

Dietary sequestration of defensive steroids in nuchal glands of the Asian snake Rhabdophis tigrinus

“…In dendrobatids, hydroxylation dramatically increases the toxicity of a sequestered alkaloid (7). The bufadienolides in R. tigrinus that have been studied for activity vary widely in their inhibition of the sodium-potassium pump and their positive inotropic action on heart muscle (29), which may be in part due to differences in hydroxylation among compounds. Hydroxylation may also influence the bioavailability of bufadienolides.…”