Calmodulin antagonists have differential effects on Ca/sup 2 +/ uptake, (Ca/sup 2 +/ + Mg/sup 2 +/)-ATPase and Ca/sup 2 +/ release in hepatic endoplasmic reticulum
The effect of calmodulin (CaM) antagonists on Ca/sup 2 +/ handling by hepatic endoplasmic reticulum (ER) was studied. Ca/sup 2 +/ uptake by saponin-permeabilized hepatocytes or isolated ER was measured using /sup 45/Ca/sup 2 +/ in a filtration assay in the presence of 0.09 ..mu..M free (Ca/sup 2 +/) and inhibitors of mitochondrial Ca/sup 2 +/ transport. Each CaM-antagonist (chlorpromazine, CPZ; trifluoperazine, TFP; calmidazolium, W7 and 48/80) showed a dose-dependent inhibition of Ca/sup 2 +/ accumulation in permeabilized hepatocytes. Both the initial rate and steady state values for Ca/sup 2 +/ uptake were reduced by 50% with 40 ..mu..M calmidazolium, 100 ..mu..M TFP, 150..mu..M W7, 150 ..mu..M CPZ and 300 ..mu..M 48/80. Using isolated ER both calmidazolium (20 ..mu..M) and W7 (150 ..mu..M) inhibited the initial rate and steady state level of Ca/sup 2 +/ accumulation. At this concentration calmidazolium inhibited the initial rate of (Ca/sup 2 +/ + Mg/sup 2 +/)-ATPase activity, and enhanced Ca/sup 2 +/ release. In contrast, W7 had no effect on these parameters. These results suggest that the reduced level of Ca/sup 2 +/ uptake into ER vesicles in the presence of calmidazolium may result from inhibition of the (Ca/sup 2 +/ + Mg/sup 2 +/)-ATPase as well as induction of Ca/sup 2 +/ release, while W7 may act to uncouple Ca/sup 2 +/ transport from its (Ca/sup 2 +/ + Mg/sup 2 +/)-ATPase counterpart.
- Research Organization:
- Washington Univ. School of Medicine, St. Louis, MO
- OSTI ID:
- 6986011
- Report Number(s):
- CONF-8606151-; TRN: 86-039069
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
- Country of Publication:
- United States
- Language:
- English
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