Interactions of chlordecone (kepone) and mirex with the nicotinic acetylcholine receptor--ion channel complex.
Interactions of chlordecone (kepone) and mirex with nicotinic acetylcholine (ACh) receptor complexes from Torpedo californica electric organs were studied using biochemical probes for ACh and ion-channel binding sites. Neither compound inhibited the binding of [125I] alpha-bungarotoxin (BGT) to the receptor; chlordecone, however, enhanced carbamylcholine affinity for the receptor 5-fold. Chlordecone, but not mirex, also inhibited the binding of [3H]perhydrohistrionicotoxin and [3H]phencyclidine to sites associated with the receptor-gated ion channel. Ion-channel inhibition by chlordecone was enhanced in the presence of carbamylcholine. These results indicate that chlordecone, but not mirex, interacts with the ion-translocation mechanism associated with nicotinic ACh receptors, where it may sterically block ion flux as well as stabilize a desensitized conformation of the receptor complex.
R S
RS
Aronstam
J S
JS
Hong
D000494:Allosteric Regulation / Q000187:drug effects; D000664:Amphibian Venoms / Q000378:metabolism; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D007631:Chlordecone / Q000494:pharmacology*; D004557:Electric Organ / Q000378:metabolism; D066298:In Vitro Techniques; D007306:Insecticides / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008917:Mirex / Q000494:pharmacology*; D010622:Phencyclidine / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D014101:Torpedo
D000664:Amphibian Venoms; D002038:Bungarotoxins; D007306:Insecticides; D007473:Ion Channels; D011978:Receptors, Nicotinic; C004792:perhydrohistrionicotoxin; D002217:Carbachol; D010622:Phencyclidine; D007631:Chlordecone; D008917:Mirex