Discrimination between nicotinic receptors in vertebrate ganglia and skeletal muscle by alpha-bungarotoxin and cobra venoms.
1. We have used snake neurotoxins, alpha-bungarotoxin and venoms from Naja naja siamensis and Naja nivea, to distinguish the nicotinic receptors of ganglia from those of skeletal neuromuscular junctions. 2. These neurotoxins failed to block responses of isolated guinea-pig longitudinal muscle with adherent myenteric plexus to the nicotinic agonists, nicotine or dimethylphenylpiperazinium, to acetylcholine (ACh), or to electrical field stimulation. 3. The toxins failed to affect responses of the isolated guinea-pig stomach to pregnaglionic stimulation by way of the vagus nerves or of the vas deferens to preganglionic stimulation via the hypogastric nerves. 4. Snake neurotoxins did not block non-adrenergic inhibitory responses of the rabbit small intestine to nicotine or electrical field stimulation. 5. Neurotoxins were ineffective blockers against nicotinic agonists in new-born rabbit or embryonic chick intestine. 6. Attempts to increase the penetration of the toxins into tissues with dimethylsulphoxide, exposure to hypertonic solutions, or to ethylene-diaminetetracetic acid did not enable the toxins to act as nicotinic antagonists. 7. In contrast to diaphragmatic or oesophageal skeletal neuromuscular junctions no binding of rhodamine or tritium labelled toxins to structures in ganglia could be detected. 8. No potential permeability barriers were found by electron microscopy of the ganglia of the guinea-pig myenteric plexus. 9. The tracers, lanthanum ion and ruthenium red, readily penetrated into all regions of the myenteric plexus including synaptic gaps. 10. It is concluded that the failure of snake neurotoxins to act as nicotinic antagonists or to bind to ganglia is not due to their inability to reach ganglionic nicotinic receptors. Therefore, it is likely that ganglionic nicotinic receptors are different from those of the skeletal neuromuscular junction.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism / Q000494:pharmacology; D005725:Ganglia, Autonomic / Q000187:drug effects*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects; D051379:Mice; D009197:Myenteric Plexus / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011817:Rabbits; D051381:Rats; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012910:Snake Venoms / Q000378:metabolism / Q000494:pharmacology*
D002038:Bungarotoxins; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D012910:Snake Venoms