EFFECTS OF TRIBUTYLTIN, DIBUTYLTIN AND MONOBUTYLTIN ON SYNAPTIC PARAMETERS OF THE CHOLINERGIC SYSTEM IN THE CEREBRAL-CORTEX OF MICE

Triorganotin compounds like tributyltin have been reported to be biode graded to diorganotin, monoorganotin and then inorganic tin in animals after they have been ingested. Effects of tributyltin, dibutyltin and monobutyltin on various cholinergic parameters that are involved in s ynaptic transmission in the mouse cerebral cortex were investigated in vitro. Tributyltin and dibutyltin, but not monobutyltin, inhibited th e activity of choline acetyltransferase, both the high-affinity and lo w-affinity uptakes of choline into synaptosomes, and the binding of [H -3]quinuclidinyl benzilate to muscarinic acetylcholine receptors. Trib utyltin and dibutyltin, but not monobutyltin, had a slightly suppressi ve effect on the K+-induced release and synthesis of acetylcholine in slices of the cortex. All three butyltins at concentrations from 10(-6 ) to 10(-4) M had no effect on the activity of acetylcholinesterase. T he extent of the inhibitory effects on the cholinergic parameters, apa rt from the activity of acetylcholinesterase, was slightly greater in the case of tributyltin than dibutyltin, in particularly at the highes t concentration (10(-4) M) tested. Therefore, it is concluded that tri butyltin metabolites inhibit various parameters of cholinergic activit y with a potency ranking of tributyltin > dibutyltin > monobutyltin.