The tyramine-labelled vesicular transporter for dopamine: a putative target of pesticides and neurotoxins.
This study defined the ability of a large sample of heterogeneous pesticides and neurotoxins to interact with the [3H]tyramine-labelled vesicular transporter of dopamine in rat striatum. Botanical (with rotenone as the most potent), and organochlorine (Kepone) insecticides, as well as fungicides (Zineb), as a whole, consistently inhibited [3H]tyramine binding, with Ki values ranging from 5 nM to 10 microM. ATP/Mg(2+)-dependent [3H]tyramine uptake to purified striatal synaptic vesicles was also inhibited by rotenone. Organophosphate and carbamate insecticides, and miscellaneous herbicides poorly antagonized [3H]tyramine binding, yielding Ki values exceeding 10 microM. Several, though not all, of the best recognized central neurotoxins tested were major binding antagonists. Their rank order of potency was 1-methyl-4-phenylpyridinium ion (MPP+) > trimethyltin > or = 6-hydroxydopamine > N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) > 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with Ki values ranging from 35 nM to 3 microM. Overall, the potent interaction of selected pesticides and chemicals with the vesicular transporter for dopamine, although, by itself, not synonymous with neurotoxicity, would argue for a likely impairment of transmitter homeostasis, or the putative formation of neurodegenerative toxin pools.
Vaccari
A
A
Department of Neuroscience B. Brodie, Medical School, University of Cagliari, Italy.
Saba
P
P
D000818:Animals; D002219:Carbamates; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology; D050483:Dopamine Plasma Membrane Transport Proteins; D005659:Fungicides, Industrial / Q000494:pharmacology; D006540:Herbicides / Q000494:pharmacology; D007306:Insecticides / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D009943:Organophosphorus Compounds; D010575:Pesticides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000494:pharmacology; D014439:Tyramine / Q000378:metabolism*
D002219:Carbamates; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D005659:Fungicides, Industrial; D006540:Herbicides; D007306:Insecticides; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D009943:Organophosphorus Compounds; D010575:Pesticides; D012402:Rotenone; D004298:Dopamine; D014439:Tyramine