Effects of organotins on the cholinergic system in the chicken brain in vitro.
The effects of two organotins, trimethyltin chloride (TMT) and tributyltin chloride (TBT), on the cholinergic system in the chicken brain were investigated in vitro. Both compounds, at concentrations below 10(-4)m, had almost no effect on acetylcholinesterase activity in cortical homogenate. By contrast, TMT and TBT inhibited non-competitively the activity of choline acetyltransferase with K(i) values of 1.5 x 10(-5) and 0.99 x 10(-5)m, as well as the high-affinity uptake of choline with K(i) values of 35 x 10(-6) and 2.5 x 10(-6)m, respectively. These inhibitory effects were not reversed in the presence of cysteine. TMT and TBT inhibited the low-affinity uptake of choline with K(i) values of 2.6 x 10(-4) and 1.25 x 10(-4)m, respectively. Although both compounds inhibited the depolarized release of acetylcholine (ACh) from slices of brain, only TBT at 10(-4)m suppressed the synthesis of ACh. TBT, but not TMT, inhibited the binding of [(3)H]quinuclidinyl benzilate, which is an indicator of muscarinic ACh receptors, at 10(-5) and 10(-4)m. It is suggested that cholinergic transmission, in particular the synthesis of ACh and the release of ACh, is susceptible to trialkylin neurotoxicity.
Kobayashi
H
H
Department of Veterinary Pharmacology, Faculty of Agriculture, Iwate University, Morioka 020, Japan.
Saito
F
F
Yuyama
A
A