Irreversible autonomic actions by lophotoxin suggest utility as a probe for both C6 and C10 nicotinic receptors.
The marine natural product lophotoxin has produced a non-reversible antagonism of parasympathetic and sympathetic functions that are known to be mediated by C6 sub-type nicotinic receptors. Transmission through anuran paravertebral ganglia was eliminated in 20-40 min by 10-30-min treatments with 16-32 microM lophotoxin, in a time course resembling the onset of block of C10 sub-type nicotinic receptors at the neuromuscular junction and in cultured BC3H-1 cells. The action persisted through 16 h of washout. Nerve conduction was unaffected. Somewhat longer treatments (80 min) of in vitro ileal sections resulted in loss of sensitivity to nicotine, but not to acetylcholine, for at least 5 h. These data indicate that lophotoxin can serve as a more universal nicotinic receptor probe than the alpha-neurotoxins, which may bind to both C6 and C10 sub-types, but block only the C10.
D000818:Animals; D002460:Cell Line; D004224:Diterpenes / Q000494:pharmacology*; D005728:Ganglia, Sympathetic / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D011817:Rabbits; D011892:Rana catesbeiana; D011894:Rana pipiens; D011950:Receptors, Cholinergic / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D013729:Terpenes
D004224:Diterpenes; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D013729:Terpenes; C030303:lophotoxin