Effects of Tri-, Di and Monobutyltin on Synaptic Parameters of the Cholinergic System in the Cerebral Cortex of Mice

Abstract

ABSTRACT-Triorganotin compounds like tributyltin have been reported to be biodegraded 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 synaptic transmission in the mouse cerebral cortex were investigated in vitro. Tributyltin and dibutyltin, but not monobutyltin, inhibited the activity of choline acetyltransferase, both the high-affinity and low-affinity uptakes of choline into synaptosomes, and the binding of [3H]quinuclidinyl benzilate to muscarinic acetylcholine receptors. Tributyltin and dibutyltin, but not monobutyltin, had a slightly suppressive 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. The extent of the inhibitory effects on the cholinergic parameters, apart from the activity of acetylcholinesterase, was slightly greater in the case of tributyltin than dibutyltin, in particularly at the highest concentration (10-4 M) tested. Therefore, it is concluded that tributyltin metabolites inhibit various parameters of cholinergic activity with a potency ranking of tributyltin > dibutyltin > monobutyltin.

Enhanced excitability and suppression of A-type K+ current of pancreas-specific afferent neurons in a rat model of chronic pancreatitis

“…There has only been one previous report (32) measuring abdominal hypersensitivity in a "chronic" model using dibutyltin to induce inflammation. However, dibutyltin affects tetrodotoxinresistant Na ϩ currents in sensory neurons in addition to its effect as a general neurotoxin (13,14,17,31), thus seriously confounding the interpretation of the findings. In contrast, the TNBS-induced model of CP is morphologically similar to human CP (construct validity) and also displays face and predictive validity, thus representing a robust experimental approach for the establishment of working paradigms to explain the pathogenesis of pain in CP.…”

Organotins in Neuronal Damage, Brain Function, and Behavior: A Short Review

“…Neurotransmitter systems are influenced by DBT intoxication, as DBT exposure decreased the levels of dopamine and serotonin in the striatum and frontal cortex, respectively, causing impairments in learning and decreased spontaneous locomotion ( 61 ). Cholinergic neurotransmission is also affected, as DBT is capable of decreasing the activity of choline acetyltransferase, the uptake of choline into synaptosomes and the myelin content of cholinergic neurons of rodents ( 62 , 63 ). As the data were obtained through in vitro experiments, the behavioral outcomes of the impaired acetylcholine neurotransmission have yet to be evaluated.…”

Modulation of the F1FO‐ATPase function by butyltin compounds

“…Finally, MBT, the last organotin derived from the stepwise debutylation of TBT, is ineffective both on the F 1 F O ‐ATPase catalytic activity and on its oligomycin sensitivity (Fig. ), thus confirming its far lower toxicity with respect to the other butyltins to a variety of enzymes such as Na,K‐ATPase, acetylcholinesterase, AMP deaminase and aromatase …”