Selective effects of cyclodiene insecticides on dopamine release in mammalian synaptosomes.
Cyclodiene insecticides release labeled neurotransmitter in striatal and cortical synaptosome preparations under nondepolarizing conditions, typically showing half-maximal potencies for release in the low micromolar range. This level of potency is similar to those reported for inhibition of 36Cl- influx at the gamma-aminobutyric acid (GABA)(A) receptor, their consensus target site. A wide variety of other GABA(A) antagonists, including picrotoxinin and bicuculline, did not cause significant dopamine release, which obviated direct involvement of the GABA(A) receptor as a possible site of action. Release assays with different transmitters indicated that striatal dopaminergic terminals are severalfold more sensitive to release than other neurotransmitter types. The selective sensitivity of nigrostriatal dopaminergic nerve terminals to insecticidal organochlorines provides biochemical evidence supporting an epidemiological linkage between exposure to environmental toxicants and Parkinsonism.
Kirby
Michael L
ML
Department of Entomology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
Barlow
Rebecca L
RL
Bloomquist
Jeffrey R
JR
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000633:toxicity*; D006533:Heptachlor / Q000633:toxicity; D007306:Insecticides / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018756:GABA Antagonists; D007306:Insecticides; D005680:gamma-Aminobutyric Acid; D006533:Heptachlor; D004298:Dopamine