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  • Title: Lophotoxin: selective blockade of nicotinic transmission in autonomic ganglia by a coral neurotoxin.
    Author: Sorenson EM, Culver P, Chiappinelli VA.
    Journal: Neuroscience; 1987 Mar; 20(3):875-84. PubMed ID: 2885781.
    Abstract:
    Lophotoxin is a diterpene lactone isolated from gorgonian corals. The toxin has previously been shown to bind with high affinity to an acetylcholine recognition site located on skeletal muscle nicotinic receptors, producing an essentially irreversible blockade of neuromuscular transmission. Lophotoxin has also been shown to block nicotinic transmission in autonomic ganglia of the frog and in ileal strips of guinea pig and rabbit. The effects of lophotoxin have now been examined on neuronal nicotinic receptors in autonomic ganglia of the chick and rat. Low concentrations of lophotoxin (1 microM) produce a blockade of neuronal nicotinic transmission which is partially reversed by 3-5 h of washing out the toxin. The blockade produced by higher concentrations of lophotoxin (up to 32 microM) is not reversed during a similar washout period. Prior exposure to d-tubocurarine, a competitive nicotinic antagonist, can partially protect ganglia against exposure to lophotoxin. In contrast the local anesthetic QX-314, a noncompetitive nicotinic antagonist, does not protect ganglia against lophotoxin exposure. Lophotoxin binds to a site in ganglia identified by [125I]kappa-bungarotoxin which appears to be on the neuronal nicotinic receptor. Intracellular recordings reveal that lophotoxin has no effect on either muscarinic responses or on responses to gamma-aminobutyrate in autonomic ganglia. Passive and active membrane properties of the neurons are unaffected by lophotoxin except for the blockade of nicotinic responses. It is concluded that lophotoxin is a selective, high-affinity antagonist at the neuronal nicotinic receptor. The long-term nature of the blockade with lophotoxin suggests that the toxin will be of considerable value as a probe for characterizing the ganglionic nicotinic receptor.
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