Short Communication Lophotoxin Blocks Synaptic Acetylcholine Receptors in the Cockroach Periplaneta Americana

The actions of lophotoxin on synaptic acetylcholine receptors were investigated, using the cholinergic synapse between the lateral filiform hair sensory neurone and giant interneurone 3 in the first-instar cockroach Periplaneta americana. Lophotoxin (1-Oxl0~moll~) blocked transmission without affecting the passive or active membrane properties of the preand postsynaptic neurones, and without affecting non-cholinergic synaptic inputs. Micromolar concentrations of lophotoxin also blocked the depolarizing response of giant interneurone 3 to carbamylcholine, when applied ionophoretically to its dendritic branches. The toxin shifted , the dose-response curve to the right by two orders of magnitude, suggesting that it was acting as a competitive antagonist. Lophotoxin is a diterpene lactone isolated from gorgonian corals of the genus Lophogorgia (Fenical et al. 1981). It has recently been shown to block nicotinic neuromuscular transmission in vertebrates at micromolar concentrations (Culver & Jacobs, 1981; Langdon & Jacobs, 1983; Atchison, Narahashi & Vogel, 1984), and binding studies have shown that it blocks transmission by binding to the acetylcholine recognition sites of muscle nicotinic receptors (Culver, Fenical & Taylor, 1984). Recently, lophotoxin has emerged as a selective, high-affinity antagonist at neuronal nicotinic receptors, blocking transmission in autonomic ganglia of the chick and rat at concentrations in the range 1-Oxl0~moll~ to 3-2xlO~moll~ (Sorenson, Culver & Chiappinelli, 1987). However, the toxin has not been tested on invertebrate nervous tissues. There is considerable evidence that cereal afferent, giant interneurone synapses of the cockroach Periplaneta americana are cholinergic (Sattelle, 1985), and the nicotinic antagonist a'-bungarotoxin blocks transmission at nanomolar concentrations (Sattelle et al. 1983). The first-instar terminal abdominal ganglion is a useful preparation for studies of axonal and synaptic physiology since the