Vagal nerve stimulation of the guinea-pig oesophagus

Vagal nerve stimulation of the isolated guinea-pig oesophagus resulted in a triphasic contractile response which was abolished by tetrodotoxin. The mechanisms for each of the three responses were investigated. The first response was abolished by the neuromuscular blocking drug, tubocurarine, and was unaffected by atropine. The second response to vagal nerve stimulation was abolished by the ganglion blocking drug, hexamethonium, and by tubocurarine at a higher concentration than that required to block the first response. The second response was also abolished by atropine and was enhanced by physostigmine. It was concluded that this response was due to preganglionic stimulation of smooth muscle. omega-Conotoxin GVIA selectively inhibited the third response. This response was resistant to the neuromuscular and ganglion blocking drugs yet was abolished by atropine and was enhanced by physostigmine. This implicates the involvement of cholinergic neurones activated independently of nicotinic ganglionic receptors. The third response was also selectively abolished by capsaicin and enhanced by thiorphan. Contractile responses resulting from exogenous substance P were abolished by atropine and tetrodotoxin and enhanced by physostigmine. These findings suggest that the third response may be mediated by the action of a substance P-like neuropeptide released from sensory nerve endings which subsequently activate cholinergic neurones.