Cytosolic and localized inhibition of phosphodiesterase by atrazine in swine tissue homogenates

Atrazine (ATR) significantly inhibited phosphodiesterase (PDE) in crude homogenates of swine heart, brain, and lung, but not liver or kidney tissues. Except for heart, PDE activities in the cytosolic fraction of the tissue homogenates were not affected by ATR. The inhibition of the PDE activity in the cytosol from heart homogenate was not significantly different between ATR and a non-specific PDE inhibitor, 3-isobutyl-1-methylxanthine (IBMX). Dixon plots of the crude tissue homogenates showed that heart and brain were inhibited via two different mechanisms (competitive or mixed inhibition, and noncompetitive inhibition, respectively), suggesting that ATR may be a semi-specific PDE inhibitor. Furthermore, in crude tissue homogenates, ATR did not inhibit PDE as effectively as IBMX suggesting that there are ATR-susceptible and ATR-nonsusceptible forms of PDE. Association constants for ATR were 55 μM for heart and 310 μM for brain. The stability of the activity of PDE was affected by freezing, requiring the use of only freshly prepared tissue homogenates.