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Effects of organotins on the cholinergic system in the chicken brain in vitro

H Kobayashi1, F Saito, A Yuyama

  • 1Department of Veterinary Pharmacology, Faculty of Agriculture, Iwate University, Morioka 020, Japan.

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|August 25, 2010
PubMed

Insights

Trimethyltin chloride (TMT) and tributyltin chloride (TBT) disrupt the brain's cholinergic system by inhibiting choline acetyltransferase and choline uptake. These organotins impair acetylcholine synthesis and release, indicating susceptibility to trialkylin neurotoxicity.

Area of Science:

  • Neuroscience
  • Toxicology
  • Biochemistry

Background:

  • The cholinergic system is crucial for neurotransmission.
  • Organotins are environmental contaminants with known neurotoxic effects.
  • Understanding organotin impact on neurotransmitter systems is vital for public health.

Purpose of the Study:

  • To investigate the in vitro effects of trimethyltin chloride (TMT) and tributyltin chloride (TBT) on the chicken brain's cholinergic system.
  • To determine the specific mechanisms by which TMT and TBT affect acetylcholine (ACh) synthesis, release, and receptor binding.

Main Methods:

  • In vitro assessment of acetylcholinesterase activity in cortical homogenates.
  • Non-competitive inhibition assays for choline acetyltransferase activity.
  • Analysis of high- and low-affinity choline uptake kinetics.
  • Measurement of acetylcholine synthesis and release from brain slices.
  • Assessment of muscarinic acetylcholine receptor binding using [(3)H]quinuclidinyl benzilate.

Main Results:

  • TMT and TBT non-competitively inhibited choline acetyltransferase and choline uptake at low concentrations.
  • Both compounds inhibited low-affinity choline uptake.
  • TMT and TBT inhibited depolarized acetylcholine release, with TBT also suppressing ACh synthesis.
  • TBT inhibited muscarinic ACh receptor binding, unlike TMT.

Conclusions:

  • Cholinergic transmission, particularly acetylcholine synthesis and release, is vulnerable to trialkylin neurotoxicity.
  • TBT exhibits a broader range of inhibitory effects on the cholinergic system than TMT.
  • These findings highlight the neurotoxic potential of organotins on critical neurotransmitter pathways.

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