Significance of skeletal muscle digitalis receptors for [3H]ouabain distribution in the guinea pig.
The importance of specific digitalis glycoside binding sites in skeletal muscle for the digitalis glycoside distribution in the guinea pig was evaluated using [3H]ouabain and [3H]digoxin binding assays. Measurements of [3H]ouabain binding capacity (EOmax) in gastrocnemius and heart muscles in vitro gave values of 474 +/- 15 and 1,092 +/- 39 pmol/g wet wt., respectively, in 4-week-old guinea pigs. Hence the total amount of [3H]ouabain binding sites in skeletal muscle and the heart was around 42,700 and 1,200 pmol, respectively. The apparent dissociation constants (Kd) for ouabain receptor interaction was 0.7 X 10(-7) and 1.5 X 10(-7) M for skeletal muscle and heart, respectively. Comparison of [3H]ouabain and [3H]digoxin binding revealed that these drugs are competitive. From birth to maturity the concentration of [3H]ouabain binding sites in guinea pigs decreased from 803 +/- 58 to 304 +/- 28 pmol/g wet wt. in gastrocnemius muscle and from 1,458 +/- 31 to 1,079 +/- 19 pmol/g wet wt. in the heart. After i.p. injection, measurements of the distribution of [3H]ouabain in plasma, skeletal muscle and the heart showed an almost equal relative specific occupancy of digitalis glycoside receptors in skeletal muscle and the heart: When 10% of the digitalis receptors in the heart were occupied by [3H]ouabain, 13% of those in the skeletal muscles were occupied. It was calculated that 1 hr after the i.p. administration of [3H]ouabain the amount of [3H]ouabain specifically bound to the skeletal muscles and the heart corresponded to 5 times and 1/10 the amount available in the extracellular pool, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Kjeldsen
K
K
Nørgaard
A
A
Hansen
O
O
Clausen
T
T
D000367:Age Factors; D000818:Animals; D004077:Digoxin / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009132:Muscles / Q000201:enzymology / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010042:Ouabain / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014316:Tritium
D011955:Receptors, Drug; C027082:digitalis receptor; D014316:Tritium; D010042:Ouabain; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase