title: Interactions of piperidine derivatives with the nicotinic cholinergic receptor complex from Torpedo electric organ.
abstract: The interactions of eight piperidine derivatives with nicotinic receptor complexes from Torpedo californica electric organ were studied using [125I] alpha-bungarotoxin [( 125I]BGT) as a probe for the acetylcholine binding site and [3H]perhydrohistrionicotoxin [( 3H]H12-HTX) as a probe for a site associated with the receptor-gated ion channel. Cis- and trans-2-methyl-6-n-undecanyl piperidines (MUP), major constituents of fire ant venom, had a high-affinity for [3H]H12-HTX binding sites (Ki = 0.08-0.24 microM), but had no affect on receptor binding. MUP affinity for [3H]H12-HTX binding sites was approximately doubled in the presence of 1 microM carbamylcholine. Introduction of a 2'-hydroxyl group to the undecanyl side channel had little effect on activity of the alkaloid. The analog 2,6- (but not 3,5-) dimethylpiperidine was a moderately active inhibitor of [3H]H12-HTX binding (Ki = 8.8 microM). 2-Methylpiperidine was considerably less active (Ki = 600 microM), although it was more potent than either 3- or 4-methylpiperidine. The affinities of 2,6-dimethylpiperidine and 2-methylpiperidine for [3H]H12-HTX binding sites were decreased in the presence of 1 microM carbamylcholine. Carbamylcholine affinity for the receptor was increased by up to 7 fold in the presence of 10 and 32 microM MUP, but was decreased in the presence of 2,6-dimethylpiperidine and 2-methylpiperidine. The cis- and trans-isomers of MUP were equipotent in producing each of its effects. In these actions, MUP resembles a variety of other compounds derived from 2,6-disubstituted piperidines, including histrionicotoxins, gephyrotoxins and pumiliotoxins.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000664:Amphibian Venoms / Q000378:metabolism; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D004557:Electric Organ / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism* / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism* / Q000502:physiology; D013329:Structure-Activity Relationship; D014101:Torpedo
chemical_list: D000664:Amphibian Venoms; D002038:Bungarotoxins; D007473:Ion Channels; D010880:Piperidines; D011978:Receptors, Nicotinic; C004792:perhydrohistrionicotoxin