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• W2021965613 abstract "The developmental neurotoxicity of chlorpyrifos (CPF) involves mechanisms over and above cholinesterase inhibition. In the present study, we evaluated the effects of gestational CPF exposure on the adenylyl cyclase (AC) signaling cascade, which regulates the production of cyclic AMP, a major controller of cell replication and differentiation. In addition to basal AC activity, we assessed the AC response to direct enzymatic stimulants [forskolin, manganese (Mn(2+))]; the response to isoproterenol, which activates signaling through beta-adrenoceptors (betaARs); and the concentration of betaAR binding sites. CPF administered to pregnant rats on gestational days (GD) 9-12 elicited little or no change in any components of AC activity or betaARs. However, shifting the treatment window to GD17-20 produced regionally selective augmentation of AC activity. In the brainstem, the response to forskolin or Mn(2+) was markedly stimulated by doses at or below the threshold for observable toxicity of CPF or for inhibition of fetal brain cholinesterase, whereas comparable effects were seen in the forebrain only at higher doses. In addition, low doses of CPF reduced betaAR binding without impairing receptor-mediated stimulation of AC. These results indicate that signal transduction through the AC cascade is a target for CPF during a discrete developmental period in late gestation, an effect that is likely to contribute to the noncholinergic component of CPF's developmental neurotoxicity." @default.
• W2021965613 created "2016-06-24" @default.
• W2021965613 creator A5000464378 @default.
• W2021965613 creator A5037296633 @default.
• W2021965613 creator A5038298482 @default.
• W2021965613 creator A5073984017 @default.
• W2021965613 date "2003-12-01" @default.
• W2021965613 modified "2023-09-28" @default.
• W2021965613 title "Developmental neurotoxicity elicited by gestational exposure to chlorpyrifos: when is adenylyl cyclase a target?" @default.
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• W2021965613 doi "https://doi.org/10.1289/ehp.6468" @default.
• W2021965613 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1241759" @default.
• W2021965613 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/14644659" @default.
• W2021965613 hasPublicationYear "2003" @default.
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