Benzamides can stimulate as well as inhibit the activity of nuclear ADP-ribosyltransferase

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Abstract
Benzamides are potent inhibitors of nuclear ADP-ribosyl-transferase and have been extensively used to demonstrate the involvement of ADP-ribosylation in cellular function. When permeabilized L1210 cells are treated with 50 μM 3-acetyl-amidobenzamide (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.