Benzamides can stimulate as well as inhibit the activity of nuclear ADP-ribosyltransferase.
Benzamides are potent inhibitors of nuclear ADP-ribosyltransferase and have been extensively used to demonstrate the involvement of ADP-ribosylation in cellular function. When permeabilized L1210 cells are treated with 50 microM 3-acetylamidobenzamide (3-aab) the enzyme is inhibited. However, when 50 nM 3-aab is used a two-fold stimulation of enzyme activity is produced. This anomalous stimulation is obtained with benzamides and nicotinamides and is correlated with their activity as inhibitors. Strikingly the steady-state level of poly(ADP-ribose) in intact cells is increased by these low levels of inhibitors. The mechanisms of this effect and its consequences for the experimental use of benzamides are discussed.
D036002:ADP Ribose Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D001549:Benzamides; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D007939:Leukemia L1210; D051379:Mice; D009243:NAD / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014407:Tumor Cells, Cultured
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; D011064:Poly Adenosine Diphosphate Ribose; C040561:3-acetamidobenzamide; D036002:ADP Ribose Transferases