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

• Published in: Toxicology in vitro Vol. 6; no. 4; p. 337
• Main Authors: Kobayashi, H, Saito, F, Yuyama, A
• Format: Journal Article
• Language: English
• Published: England 01.07.1992
• ISSN: 0887-2333
• DOI: 10.1016/0887-2333(92)90023-k

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.