Kerr K P, Mitchelson F, Coupar I M
School of Pharmacology, Victorian College of Pharmacy, Monash University, Australia.
Acta Physiol Scand. 1995 Jun;154(2):213-20. doi: 10.1111/j.1748-1716.1995.tb09903.x.
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.
对分离的豚鼠食管进行迷走神经刺激会产生一种三相收缩反应,该反应可被河豚毒素消除。对这三种反应各自的机制进行了研究。第一种反应可被神经肌肉阻断药物筒箭毒碱消除,且不受阿托品影响。对迷走神经刺激的第二种反应可被神经节阻断药物六甲铵以及浓度高于阻断第一种反应所需浓度的筒箭毒碱消除。第二种反应也可被阿托品消除,并被毒扁豆碱增强。得出的结论是,这种反应是由于节前神经对平滑肌的刺激所致。ω-芋螺毒素GVIA选择性地抑制了第三种反应。这种反应对神经肌肉和神经节阻断药物具有抗性,但可被阿托品消除,并被毒扁豆碱增强。这表明涉及到独立于烟碱型神经节受体而被激活的胆碱能神经元。第三种反应也被辣椒素选择性地消除,并被硫氧还蛋白增强。由外源性P物质引起的收缩反应可被阿托品和河豚毒素消除,并被毒扁豆碱增强。这些发现表明,第三种反应可能是由感觉神经末梢释放的一种P物质样神经肽的作用介导的,该神经肽随后激活胆碱能神经元。