A pertussis toxin-sensitive 8-lipoxygenase pathway is activated by a nicotinic acetylcholine receptor in Aplysia neurons

Acetylcholine (ACh) activates two types of chloride conductances in Aplysia neurons that can be distinguished by their kinetics and pharmacology. One is a rapidly desensitizing current that is blocked by alpha -conotoxin-ImI and the other is a sustained current that is insensitive to the toxin. Thes e currents are differentially expressed in Aplysia neurons. We report here that neurons that respond to ACh with a sustained chloride conductance also generate 8-lipoxygenase metabolites. The sustained chloride conductance an d the activation of 8-lipoxygenase have similar pharmacological profiles. B oth are stimulated by suberyldicholine and nicotine, and both are inhibited by alpha -bungarotoxin. Like the sustained chloride conductance, the activ ation of 8-lipoxygenase is not blocked by alpha -conotoxin-ImI. In spite of the similarities between the metabolic and electrophysiological responses, the generation of 8-lipoxygenase metabolites does not appear to depend on the ion current since an influx of chloride ions is neither necessary nor s ufficient for the formation of the lipid metabolites. In addition, the appl ication of pertussis toxin blocked the ACh-activated release of arachidonic acid and the subsequent production of 8-lipoxygenase metabolites, yet the ACh-induced activation of the chloride conductance is not dependent on a G protein. Our results are consistent with the idea that the nicotinic ACh re ceptor that activates the sustained chloride conductance can, independent o f the chloride ion influx, initiate lipid messenger synthesis.