Endogenous marinobufagenin-like immunoreactive substance. A possible endogenous Na, K-ATPase inhibitor with vasoconstrictor activity.
Vasoconstrictor and Na/K pump inhibitory properties of a bufodienolide Na/K-ATPase inhibitor, marinobufagenin, were studied in isolated rings of 2 to 3 order branches of human pulmonary arteries respectively. Marinobufagenin displayed concentration-dependent vasoconstrictor activity (0.01 to 10 mmol/L). In sarcolemma membranes prepared from pulmonary artery marinobufagenin inhibited Na/K-ATPase (IC50 = 50 nmol/L). In eight healthy male Caucasians, concentrations of marinobufagenin-like immunoreactive material in C-18 extracted plasma were 1.38 +/- 0.60 nmol/L. Twenty-four-hour urinary release of marinobufagenin-like immunoreactive material in eight healthy males was 1.20 +/- 0.95 nmol/day. Chloroform extract of human urine was fractionated using reverse-phase high-performance liquid chromatography (32% acetonitrile, Deltapak). The HPLC fraction coeluting with marinobufagenin in 7 min, cross reacted with antimarinobufagenin and antidigoxin, but not antiouabain antibody. These results demonstrate that human plasma and urine contains a bufodienolide vasoconstrictor EDLF, marinobufagenin-like immunoreactive Na,K pump inhibitor.
Laboratory of Pharmacology, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia.
A Y
AY
Bagrov
R I
RI
Dmitrieva
O V
OV
Fedorova
G P
GP
Kazakov
N I
NI
Roukoyatkina
V M
VM
Shpen
D002018:Bufanolides / Q000032:analysis / Q000276:immunology* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000032:analysis / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000032:analysis / Q000276:immunology* / Q000494:pharmacology
D002018:Bufanolides; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; C093896:marinobufagenin; D000254:Sodium-Potassium-Exchanging ATPase