ABSTRACT
Trifluoperazine, a drug that binds to Ca2+-calmodulin and inhibits its interaction with other proteins, was found to inhibit growth and phagocytosis in a macrophagelike cell line, J774.16. Both effects were reversible and occurred at the same concentrations of drug (25--50 microM) that inhibited the activation of cyclic nucleotide phosphodiesterase by calmodulin in vitro. Fc-mediated phagocytosis was also depressed by W-7, a sulfonamide derivative that inhibits the activity of Ca2+-calmodulin. In contrast, taxol, a drug that stabilizes cellular microtubules, had no effect on Fc-mediated phagocytosis although it inhibited cell growth at nanomolar concentrations. The inhibitory effects of trifluoperazine and W-7 on phagocytosis suggest that calmodulin may be involved in this complex cellular function.
Subject(s)
Calcium-Binding Proteins/antagonists & inhibitors , Calmodulin/antagonists & inhibitors , Macrophages/physiology , Phagocytosis/drug effects , Trifluoperazine/pharmacology , Alkaloids/pharmacology , Animals , Cell Division/drug effects , Cell Line , Cell Survival/drug effects , Mice , Muramidase/metabolism , Paclitaxel , Sulfonamides/pharmacologySubject(s)
3',5'-Cyclic-AMP Phosphodiesterases/metabolism , Calcium-Binding Proteins/metabolism , Calmodulin/metabolism , Macrophages/metabolism , Trifluoperazine/pharmacology , 3',5'-Cyclic-AMP Phosphodiesterases/isolation & purification , Animals , Calcium/pharmacology , Calmodulin/isolation & purification , Cell Division/drug effects , Cell Line , Cyclic AMP/metabolism , Genetic Variation , Kinetics , Lymphoma, Large B-Cell, Diffuse , Mice , Myosin-Light-Chain Kinase , Phagocytosis/drug effects , Protein Kinases/metabolismABSTRACT
Tunicamycin, an antibiotic that inhibits protein glycosylation, elicited a rapid depletion of insulin binding activity at the surface of 3T3-L1 adipocytes. Disappearance of insulin receptors occurred more rapidly in the presence of tunicamycin than when protein synthesis was inhibited by cycloheximide and was accompanied by a diminution in sensitivity of the adipocytes to the acute effects of insulin and anti-insulin receptor antibody on hexose uptake and metabolism.
