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Calmodulin-stimulated plasma membrane (Ca2+ + Mg2+)-ATPase: inhibition by calcium channel entry blockers.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 1987 Aug 01; Vol. 36 (15), pp. 2455-9. - Publication Year :
- 1987
-
Abstract
- Calcium channel entry blockers representing different structural classes were studied for their effects on human erythrocyte basal and calmodulin-stimulated (Ca2+ + Mg2+)-ATPase. Effects on the activity of (Mg2+)-ATPase and (Na+ + K+)-ATPase were also assessed. Of the four Ca2+ entry blockers tested, only verapamil and diltiazem specifically inhibited the calmodulin-stimulated (Ca2+ + Mg2+)-ATPase activity, the basal enzyme activity being unaltered by these drugs. Other membrane-associated ATPases were not affected. Calmodulin concentration effect curves showed the inhibition by verapamil (10(-3) M) and diltiazem (10(-3) M) to be non-competitive. This concentration inhibited the calmodulin-dependent increment (5.1 nM calmodulin) of the ATPase activity by 35 and 36% respectively. Similarly, both drugs inhibited the Ca2+-activation process of calmodulin-stimulated activity in a non-competitive manner, decreasing Vmax by 23 and 17% respectively. Basal (Ca2+ + Mg2+)-ATPase activity was not affected by verapamil or diltiazem at any calcium concentration. In contrast, cinnarizine non-specifically inhibited all four membrane ATPases including calmodulin-stimulated (Ca2+ + Mg2+)-ATPase activity at concentrations above 3 X 10(-6) M. Nifedipine was without effect on any of the four membrane ATPases. From this we conclude that certain calcium channel entry blockers can inhibit calmodulin-regulated plasma membrane Ca2+-pump ATPase. Therefore, this identifies an additional functional low affinity receptor in the plasma membrane for some of the calcium channel entry blockers.
- Subjects :
- Ca(2+) Mg(2+)-ATPase antagonists & inhibitors
Calcium-Transporting ATPases antagonists & inhibitors
Cinnarizine pharmacology
Diltiazem pharmacology
Humans
Kinetics
Sodium-Potassium-Exchanging ATPase metabolism
Verapamil pharmacology
Ca(2+) Mg(2+)-ATPase blood
Calcium Channel Blockers pharmacology
Calcium-Transporting ATPases blood
Calmodulin metabolism
Erythrocyte Membrane enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-2952
- Volume :
- 36
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 3038124
- Full Text :
- https://doi.org/10.1016/0006-2952(87)90516-8