Vipoxin both activates and antagonizes three types of acetylcholine response in Aplysia neurons

The effects of vipoxin, a 13,000 Dalton protein component of Russell's viper venom on responses of voltage-clamped Aplysia neurons to acetylcholine (ACh) and monoamines has been studied. At low doses vipoxin reversibly antagonizes all 3 types of ionic response to ACh or carbachol, the order of susceptibility to blockade being Na+ greater than K+ greater than Cl-. High doses of vipoxin directly evoke the same ionic response on a given cell as that evoked by ACh. Responses to vipoxin are reversibly antagonized by cholinergic antagonists (e.g. hexamethonium, tetraethylammonium), but not by monoamine antagonists (e.g. bufotenine, ergometrine, cimetidine). In addition to activation of cholinergic responses, high doses of vipoxin also produce a reversible potentiation of responses to dopamine and 5-hydroxytryptamine on some cells. In contrast to its effects on Aplysia neurons, vipoxin has neither agonist nor antagonist actions at the frog neuromuscular junction. These results suggest that this venom protein acts as a partial agonist at molluscan ACh receptors and provides evidence for some phylogenetic difference between molluscan and vertebrate ACh receptors.