Effects of tri-, di- and monobutyltin on synaptic parameters of the cholinergic system in the cerebral cortex of mice.
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.
Kobayashi
H
H
Department of Veterinary Pharmacology, Faculty of Agriculture, Iwate University, Morioka, Japan.
Suzuki
T
T
Kasashima
Y
Y
Motegi
A
A
Sato
I
I
Matsusaka
N
N
Ono
N
N
Miura
A
A
Saito
F
F
Saito
S
S
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D002794:Choline / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018721:Muscarinic Agonists / Q000378:metabolism; D009947:Organotin Compounds / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000201:enzymology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000187:drug effects* / Q000201:enzymology; D014220:Trialkyltin Compounds / Q000494:pharmacology*
D018721:Muscarinic Agonists; D009947:Organotin Compounds; D011976:Receptors, Muscarinic; D014220:Trialkyltin Compounds; C056189:di-n-butyltin; C011559:tributyltin; D011813:Quinuclidinyl Benzilate; D000110:Acetylcholinesterase; C020735:dibutyldichlorotin; D002794:Choline