Characterization of [3H]-nitrendipine binding to uterine smooth muscle plasma membrane and its relevance to inhibition of calcium entry.
Specific, high affinity (KD = 164 pM) binding of the Ca channel inhibitor [3H]-nitrendipine was identified in plasma membrane-enriched fractions from the rat myometrium. Although dihydropyridines effectively competed for [3H]-nitrendipine binding sites, both verapamil and D600 were poor competitors. Diltiazem (10 microM) increased [3H]-nitrendipine binding by about 40%, but had no effect on binding affinity. Among several other drugs tested, diethylstilboestrol (DES) caused a considerable inhibition of binding, with an IC50 value of 4 microM. Both La3+ and EDTA (or EGTA) inhibited binding. The inhibition by the latter could be overcome by the addition of Ca2+ or Mg2+. A clear relationship was found between [3H]-nitrendipine binding and 5-nucleotidase activity in the various subcellular fractions. Data on K+-stimulated Ca2+ influx in the intact uterine strips showed a good agreement between the inhibition by both nitrendipine and DES of stimulated Ca influx and their inhibitory effect on [3H]-nitrendipine binding to plasma membrane. This type of correlation was lacking in the case of D600. These results suggest that Ca channels in the myometrial membrane possess multiple sites at which different drugs can act to block these channels.
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D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism*; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism; D004054:Diethylstilbestrol / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D007473:Ion Channels / Q000187:drug effects*; D009130:Muscle, Smooth / Q000166:cytology*; D009539:Nicotinic Acids / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism; D009553:Nimodipine; D009568:Nitrendipine; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014599:Uterus / Q000378:metabolism*
D007473:Ion Channels; D009539:Nicotinic Acids; D004533:Egtazic Acid; D009553:Nimodipine; D004054:Diethylstilbestrol; D009568:Nitrendipine; D004492:Edetic Acid; D004110:Diltiazem; D009543:Nifedipine; D011188:Potassium; D002118:Calcium