Inhibition of cyclic AMP accumulation in dog heart washed particle preparations by aprotinine.

The effect of aprotinine, a natural non-specific protease inhibitor, on cyclic AMP accumulation in a dog heart washed particle preparation was studied. Aprotinine inhibited GTP-stimulated cyclic AMP accumulation at concentrations equal to or higher than 40 KIU/ml (8 x 10(-7) M). Aprotinine inhibited epinephrine (10(-4) M)-stimulated cyclic AMP accumulation to a greater degree than fluoride (10(-2) M)-stimulated activity. Trypsin stimulated cyclic AMP accumulation at low concentrations (0.5 to 2.5 microgram/ml) and inhibited at higher concentrations. Aprotinine at low concentrations (4 KIU/ml) inhibited the trypsin (1 microgram/ml) stimulation of cyclic AMP accumulation. We conclude that aprotinine may act on the regulator rather than on the catalytic sub-unit of adenylate cyclase and that its mechanism of action is not due only to its antiprotease activity.