Recent studies have indicated that organophosphorus pesticides (OPs) may disrupt metabolism by altering the expression or function of adenylyl cyclase (AC; the enzyme that catalyzes the formation of cAMP from ATP) or G-proteincoupled receptors and G-proteins involved in the AC signaling cascade. Such actions may alter hepatic and cardiac development and function in addition to impacting the central nervous system. However, underlying mechanisms and effects of OPs on AC signaling may differ among individual OP chemicals. Adigun et al. (p. 210) assessed effects of early life exposure to toxicologically equivalent doses of diazinon (DZN) and parathion (PRT) on the development of hepatic and cardiac cell signaling mediated through the AC cascade. The authors report that both compounds altered the developmental trajectory of AC-mediated signaling, resulting in a net gain of function that was more pronounced in the liver than in the heart. However, PRT and DZN differed with regard to the timing of their effects on hepatic AC signaling, with more pronounced effects of PRT in adolescence and more pronounced effects of DZN in adulthood. The authors conclude that results confirm variable effects of OPs on AC signaling in peripheral tissues and suggest that developmental effects of OPs on metabolism might contribute to diabetes and obesity in humans.

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