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A Convenient Method for Extraction and Analysis with High-Pressure Liquid Chromatography of Catecholamine Neurotransmitters and Their Metabolites
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Potential mechanisms responsible for chlorotriazine-induced alterations in catecholamines in pheochromocytoma (PC12)

Parikshit C Das1, William K McElroy, Ralph L Cooper

  • 1Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA. das.parikshit@epa.gov

Life Sciences
|October 11, 2003
PubMed

Insights

Chlorotriazines like atrazine and simazine reduce catecholamine synthesis by decreasing tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DbetaH) protein levels. Cyanazine, however, increases these enzyme levels, impacting dopamine and norepinephrine production.

Area of Science:

  • Neuroscience
  • Toxicology
  • Biochemistry

Background:

  • Chlorotriazines are herbicides known to affect cellular processes.
  • Previous studies indicated chlorotriazines modulate catecholamine synthesis and release in PC12 cells.
  • The specific mechanisms underlying these effects remained undetermined.

Purpose of the Study:

  • To investigate the impact of atrazine, simazine, and cyanazine on catecholamine synthesis enzymes.
  • To elucidate the intracellular pathways involved in chlorotriazine-induced modulation of catecholamine synthesis and release.
  • To determine the effects on protein expression of tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DbetaH).

Main Methods:

  • PC12 cells were incubated with atrazine, simazine, and cyanazine (100 microM).
  • Protein expression of TH and DbetaH was measured after 12-36 hours.
  • Effects on dopamine (DA) and norepinephrine (NE) concentrations and release were assessed.
  • Interactions with TH co-factors and agents affecting TH/DbetaH activity were examined.

Main Results:

  • Atrazine and simazine decreased intracellular DA, NE, and NE release, along with TH (~20%) and DbetaH (~50% and ~25%) protein expression.
  • Cyanazine increased intracellular and released NE, and significantly elevated TH (~20%) and DbetaH (~225%) protein expression.
  • TH co-factors did not alter cellular DA; agents enhancing TH/DbetaH reversed atrazine/simazine inhibition.
  • Cyanazine counteracted the NE-depleting effect of alpha-Methyl-p-tyrosine (alphaMpT).

Conclusions:

  • Chlorotriazines differentially alter dopamine and norepinephrine synthesis in PC12 cells.
  • These alterations are mediated by changes in the protein expression of key synthetic enzymes, TH and DbetaH.
  • The findings suggest distinct mechanisms of action for different chlorotriazines on catecholamine pathways.

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