Inhibitory effect of calcium-binding protein regucalcin on Ca2+/calmodulin-dependent cyclic nucleotide phosphodiesterase activity in rat liver cytosol.
The effect of regucalcin, a calcium-binding protein isolated from rat liver cytosol, on Ca2+/calmodulin-dependent cyclic nucleotide (AMP) phosphodiesterase activity in rat liver cytosol was investigated. The addition of Ca2+ (50 microM) and calmodulin 160 U/ml in the enzyme reaction mixture caused a significant increase in cyclic AMP phosphodiesterase activity. This increase was inhibited by the presence of regucalcin (0.5-3.0 microM); the inhibitory effect was complete at 1.0 microM. Regucalcin (1.0 microM) did not have an appreciable effect on basal activity without Ca2+ and calmodulin. The inhibitory effect of regucalcin was still evident even at several fold higher concentrations of calmodulin (160-480 U/ml). However, regucalcin (1.0 microM) did not inhibit Ca2+/calmodulin-dependent cyclic AMP phosphodiesterase activity in the presence of 100 and 200 microM Ca2+ added. Meanwhile, Cd2+ (25-100 microM)-induced decrease in Ca2+/calmodulin-dependent cyclic AMP phosphodiesterase activity was not reversed by the presence of regucalcin (1.0 microM). The present results suggest that regucalcin can regulate Ca2+/calmodulin-dependent cyclic AMP phosphodiesterase activity due to binding Ca2+ in liver cells.
Yamaguchi
M
M
Department of Environmental Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Tai
H
H
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D002147:Calmodulin / Q000494:pharmacology; D002265:Carboxylic Ester Hydrolases; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D015238:Sulfotransferases; D015032:Zinc / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D047908:Intracellular Signaling Peptides and Proteins; D015238:Sulfotransferases; C028152:alcohol sulfotransferase; D002265:Carboxylic Ester Hydrolases; C513325:Rgn protein, rat; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015032:Zinc; D002118:Calcium