Specific binding of cardiac glycoside drugs and endogenous digitalis-like substances to particulate membrane fractions from human placenta.
We studied the characteristics of binding of cardiac glycosides to particulate membrane fractions from human placenta, to demonstrate that placental tissue is a suitable source of receptors for digitalis drugs. Moreover, we performed preliminary experiments with 125I-labeled digoxin and placental particulates to develop a radioreceptor assay for measurement of endogenous substances with activity similar to cardiac glycoside drugs (EDLS). Placental membrane fractions were incubated with [3H]ouabain (10 nmol/L) or 125I-labeled digoxin (50 pmol/L). With both ligands, binding followed a pseudo-first-order reaction kinetics and was saturable. Scatchard analysis revealed a single class of sites [for ouabain, KD = 20.2 +/- 5.8 nmol/L (mean +/- SEM), Bmax = 3.1 +/- 0.9 nmol per gram of protein; for digoxin, KD = 29.7 +/- 1.9 nmol/L, Bmax = 24.3 +/- 1.1 nmol per gram of protein]. As expected, digoxin was less potent than ouabain in displacing both tracers from digitalis drugs receptors; progesterone, cortisone, digitoxose, furosemide, bumetanide, and propranolol had no or little effect. Specific 125I-labeled digoxin binding was competitively inhibited by plasma and (or) urine extracts from newborns, adults, pregnant women, and patients with renal insufficiency. Inhibition of binding and volume of plasma and urine assayed were linearly related. These findings support the hypothesis that cardiac glycosides and EDLS can interact with the human placenta and suggest placental tissue to be a suitable source of receptors for cardiac glycosides.
Paci
A
A
C.N.R. Institute of Clinical Physiology, University of Pisa, Italy.
Cocci
F
F
Piras
F
F
Ciarimboli
G
G
Clerico
A
A
D001665:Binding Sites / Q000187:drug effects; D001798:Blood Proteins / Q000032:analysis* / Q000652:urine; D002298:Cardenolides; D002301:Cardiac Glycosides / Q000032:analysis* / Q000097:blood / Q000652:urine; D003348:Cortisone / Q000494:pharmacology; D004077:Digoxin / Q000494:pharmacology; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010920:Placenta / Q000032:analysis*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011869:Radioligand Assay; D011955:Receptors, Drug / Q000032:analysis*; D012503:Saponins; D000254:Sodium-Potassium-Exchanging ATPase; D013347:Subcellular Fractions / Q000032:analysis
D001798:Blood Proteins; D002298:Cardenolides; D002301:Cardiac Glycosides; D011955:Receptors, Drug; D012503:Saponins; C027082:digitalis receptor; C034504:digoxin-like factors; D011374:Progesterone; D010042:Ouabain; D004077:Digoxin; D005665:Furosemide; D011433:Propranolol; D000254:Sodium-Potassium-Exchanging ATPase; D003348:Cortisone; D009638:Norepinephrine