Atrazine is a competitive inhibitor of phosphodiesterase but does not affect the estrogen receptor.

Atrazine (ATR), 2-chloro-4-ethylamino-6-isopropylamino-s-triazine, has been implicated in numerous studies to act as an endocrine disruptor, specifically by altering estradiol signaling via increased aromatase activity. Fluorescence polarization (FP) was used to show that the binding equilibria between estrogen receptor-alpha or estrogen receptor-beta, and estradiol were not affected by ATR and its metabolites: ATR-desethyl (ADE), ATR-desisopropyl (ADI), ATR-desethyldesisopropyl (ADD) and terbuthylazine (TBZ). Therefore, ATR and its degradation products were studied to determine their ability to inhibit phosphodiesterase (PDE), the enzyme responsible for hydrolyzing the second messenger cAMP to 5'-AMP. Using FP, it was found that ATR inhibited PDE with an IC50 value of 1.8 microM. This was lower than the known PDE inhibitor isobutyl methylxanthine (IBMX), which had an IC50 value of 4.6 microM. The ATR degradation products ADE, ADI, ADD and TBZ were less effective than ATR at inhibiting PDE when assayed using FP. Classical competitive binding assays, using radiolabeled 14C-cAMP in conjunction with thin layer chromatography (TLC), were used to determine that ATR was a competitive inhibitor of PDE with an association constant of 85 microM.