Amphiporus alkaloid multiplicity implies functional diversity:: initial studies on crustacean pyridyl receptors

Some hoplonemertines contain pyridyl alkaloids which are used for prey capture and chemical defense against predators. The first such alkaloid to be identified was anabaseine, a tetrahydro-bipyridyl isolated from the peregrine hoplonemertine Paranemertes peregrina Coe. Several Amphiporus species have also been shown to possess related pyridyl alkaloids. The chevron hoplonemertine Amphiporus angulatus (Fabricius) contains a particularly diverse group of bipyridyl and tetrapyridyl compounds. 2,3'-bipyridyl, a fully aromatic analog of anabaseine, is the major paralytic toxin (Kem et al., 1976). It is even more potent in paralyzing crustaceans than anabaseine, but appears to be inactive on vertebrates. We have synthesized a number of 2,3-bipyridyl analogs and tested their ability to paralyze the freshwater crayfish Procambarus clarkii Girard. A structure-activity relationship (SAR) was found that resembles the SAR for activation of vertebrate nicotinic receptors by methylated nicotine and anabaseine compounds. This suggests that 2,3'-bipyridyl, though lacking a positive charge at physiological pH, still acts as a nicotinic agonist in crustaceans. 2,3'-bipyridyl and anabaseine stimulate crustacean dactyl neuron pyridyl chemoreceptors at muM concentrations. Nemertelline, as well as these two compounds, was found to activate crayfish stomach muscle nicotinic receptors modulating chloride channels at sub-micomolar concentrations. We suggest that some amphiporid pyridyl alkaloids may deter predators not only by their central neurotoxic (paralytic) actions, but also by peripheral effects on pyridyl receptors affecting prey capture and digestion. A multiplicity of alkaloids probably provides the hoplonemertine with a variety of offensive and defensive chemical responses to the presence of other animals.