Allethrin interactions with the nicotinic acetylcholine receptor channel.
Interactions of the synthetic pyrethroid allethrin with the nicotinic acetylcholine (ACh) receptor/channel were studied in membranes from Torpedo electric organ. Allethrin did not inhibit binding of [3H]ACh to the receptor sites, but inhibited noncompetitively binding of [3H]perhydrohistrionicotoxin ([3H]H12-HTX) to the ionic channel sites in a dose-dependent manner. The inhibition constant (Ki) of [3H]H12-HTX binding in absence of receptor agonist was 30 micro M, while in presence of 100 micro M carbamylcholine it was 4 micro M. This inhibitory effect of allethrin had a negative temperature coefficient. The high affinity binding of allethrin to the channel sites of the nicotinic ACh-receptor may be indicative of a postsynaptic site of action for pyrethroids, in addition to their known action on the sodium channel.
D000109:Acetylcholine / Q000378:metabolism; D000487:Allethrins / Q000378:metabolism* / Q000494:pharmacology; D000495:Allosteric Site / Q000187:drug effects; D000664:Amphibian Venoms / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002217:Carbachol / Q000494:pharmacology; D004557:Electric Organ / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism; D010276:Parasympatholytics / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013696:Temperature; D014101:Torpedo / Q000378:metabolism*
D000487:Allethrins; D000664:Amphibian Venoms; D007473:Ion Channels; D009498:Neurotoxins; D010276:Parasympatholytics; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; C004792:perhydrohistrionicotoxin; D002217:Carbachol; D000109:Acetylcholine