Abstract
The effect of the isoquinoline derivative, drotaverine on the specific binding of [(3)H]nitrendipine and [(3)H]diltiazem to pregnant rat uterine membranes was examined. Drotaverine inhibited the specific [(3)H]nitrendipine and [(3)H]diltiazem bindings with IC(50) values of 5.6 and 2.6 microM, respectively. Saturation studies showed that diltiazem caused a significant increase in the maximum binding density without changing the K(D) of [(3)H]nitrendipine while drotaverine increased both the K(D) and the B(max) of [3H]nitrendipine. The dissociation kinetics of both [3H]nitrendipine and [(3)H]diltiazem were accelerated by drotaverine. These results suggest that drotaverine has a negative allosteric interaction with the binding sites for 1,4-dihydropyridines and 1,5-benzothiazepines on the L-type Ca(2+) channel in pregnant rat uterine membranes, which may have implications as to the potential usefulness of this drug in aiding child delivery.
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
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Animals
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Binding, Competitive / drug effects
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Calcium Channel Blockers / metabolism
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Calcium Channel Blockers / pharmacology*
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Calcium Channels, L-Type / drug effects*
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Calcium Channels, L-Type / metabolism
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Diltiazem / metabolism
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Diltiazem / pharmacology
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Female
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Half-Life
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In Vitro Techniques
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Kinetics
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Membranes / drug effects
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Membranes / metabolism
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Nitrendipine / metabolism
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Nitrendipine / pharmacology
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Papaverine / analogs & derivatives*
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Papaverine / metabolism
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Papaverine / pharmacology*
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Parasympatholytics / pharmacology
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Phosphodiesterase Inhibitors / pharmacology
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Pregnancy
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Pregnancy, Animal / physiology*
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Uterus / drug effects
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Uterus / metabolism*
Substances
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Calcium Channel Blockers
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Calcium Channels, L-Type
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Parasympatholytics
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Phosphodiesterase Inhibitors
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drotaverin
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Nitrendipine
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Papaverine
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3',5'-Cyclic-AMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Diltiazem