Neonatal organophosphorus pesticide exposure alters the developmental trajectory of cell-signaling cascades controlling metabolism: differential effects of diazinon and parathion.

Environmental Health Perspectives
Abayomi A AdigunT A Slotkin

Abstract

Organophosphorus pesticides (OPs) are developmental neurotoxicants but also produce lasting effects on metabolism. We administered diazinon (DZN) or parathion (PRT) to rats on postnatal days 14 at doses straddling the threshold for systemic signs of exposure and assessed the effects on hepatic and cardiac cell signaling mediated through the adenylyl cyclase (AC) cascade. In the liver, DZN elicited global sensitization, characterized by parallel up-regulation of AC activity itself and of the responses to stimulants acting at beta-adrenergic receptors, glucagon receptors, or G-proteins. The effects intensified over the course from adolescence to adulthood. In contrast, PRT elicited up-regulation in adolescence that waned by adulthood. Superimposed on these general patterns were effects on glucagon receptor coupling to AC and on responses mediated through the Gi inhibitory protein. The effects on the liver were more substantial than those in the heart, which displayed only transient effects of DZN on AC function in adolescence and no significant effects of PRT. Furthermore, the hepatic effects were greater in magnitude than those in a brain region (cerebellum) that shares similar AC cascade elements. These findings indicate that O...Continue Reading

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Citations

Apr 24, 2014·Current Diabetes Reports·Andrew G Kirkley, Robert M Sargis
Feb 3, 2012·Environmental Health Perspectives·Kristina A ThayerMichael A Gallo
Feb 27, 2015·Environmental Monitoring and Assessment·Maria G C YuantariMuhammad N Shobib
Jun 10, 2014·Journal of Biochemical and Molecular Toxicology·Jonggun KimYeonhwa Park
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Sep 26, 2015·Current Environmental Health Reports·Yun Liu, Karen E Peterson
Dec 12, 2012·Journal of Agricultural and Food Chemistry·Yooheon ParkYeonhwa Park

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