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胆碱能阻断、肾上腺素能阻断及交感神经去神经支配对豚鼠胃肠道肌电活动的影响

Effects of cholinergic blockade, adrenergic blockade and sympathetic denervation on gastrointestinal myoelectric activity in guinea pig.

作者信息

Galligan J J, Furness J B, Costa M

出版信息

J Pharmacol Exp Ther. 1986 Sep;238(3):1114-25.

PMID:2875169
Abstract

Gastrointestinal myoelectric activity was recorded from conscious guinea pigs using sets of bipolar electrodes that had been surgically implanted onto the serosal surface of the gastric antrum or small intestine. The role of nerves in the control of the migrating myoelectric complex (MMC) was investigated using cholinergic and adrenergic receptor antagonists, guanethidine to block sympathetic transmission, reserpine to deplete intestinal monoamines and 6-hydroxydopamine (6-OHDA) to produce chemical sympathectomy and surgical sympathetic denervation of the stomach and small intestine. Subcutaneous infusion of hyoscine (1.0 or 3.0 mg/kg and 1.0 or 3.0 mg/kg/hr) blocked the initiation of phase 3 of the MMC. In the presence of hyoscine, intermittent electrical spiking comparable to that of phase 2 of the MMC was recorded. Hexamethonium infusion (3.0 or 10.0 mg/kg and 3.0 or 10.0 mg/kg/hr) also blocked the initiation of phase 3 and reduced the frequency of the intermittent spiking activity. Acute blockade of adrenergic receptors by simultaneous s.c. infusion of phentolamine and propranolol (1.0 mg/kg and 1.0 mg/kg/hr of each drug) did not alter the MMC, whereas infusion of guanethidine (3.75 or 7.5 mg/kg and 3.75 or 7.5 mg/kg/hr) increased the frequency of the MMC by significantly shortening the duration of phase 2. Sympathetic denervation of the stomach and small intestine did not block the MMC but decreased the cycle frequency by significantly prolonging the duration of phase 2. Chemical sympathectomy using 6-OHDA treatment (3 X 250 mg/kg s.c.) also did not abolish the MMC but decreased the frequency by increasing the duration of phase 2. Reserpine treatment (2.5 mg/kg s.c.) decreased the frequency of the MMC to a greater extent than that produced by 6-OHDA treatment. Histochemical and immunohistochemical evaluation of tissues taken from denervated, 6-OHDA- and reserpine-treated animals confirmed that surgical denervation removed sensory and adrenergic nerves to the stomach and small intestine, whereas chemical sympathectomy affected only adrenergic neurons. Reserpine treatment depleted norepinephrine from extrinsic adrenergic neurons and also depleted 5-hydroxytryptamine from intrinsic intestinal neurons. In the guinea pig, antral myoelectric activity is briefly inhibited during duodenal phase 3. Gastric inhibition persisted during duodenal phase 3 in surgically denervated animals, in 6-OHDA-treated animals and in animals treated acutely with guanethidine. These results indicate that extrinsic sensory and sympathetic nerves are not required for the initiation and propagation of the MMC in the guinea pig small intestine.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

使用一组双极电极记录清醒豚鼠的胃肠肌电活动,这些电极已通过手术植入胃窦或小肠的浆膜表面。使用胆碱能和肾上腺素能受体拮抗剂、胍乙啶阻断交感神经传递、利血平耗尽肠道单胺以及6-羟基多巴胺(6-OHDA)进行化学性交感神经切除术和对胃和小肠进行手术性交感神经去支配,研究神经在控制移行性肌电复合波(MMC)中的作用。皮下注射东莨菪碱(1.0或3.0mg/kg以及1.0或3.0mg/kg/小时)可阻断MMC第3相的起始。在存在东莨菪碱的情况下,记录到了与MMC第2相类似的间歇性电尖峰。注入六甲铵(3.0或10.0mg/kg以及3.0或10.0mg/kg/小时)也可阻断第3相的起始并降低间歇性尖峰活动的频率。同时皮下注射酚妥拉明和普萘洛尔(每种药物1.0mg/kg以及1.0mg/kg/小时)急性阻断肾上腺素能受体并未改变MMC,而注入胍乙啶(3.75或7.5mg/kg以及3.75或7.5mg/kg/小时)通过显著缩短第2相的持续时间增加了MMC的频率。对胃和小肠进行交感神经去支配并未阻断MMC,但通过显著延长第2相的持续时间降低了周期频率。使用6-OHDA处理(3×250mg/kg皮下注射)进行化学性交感神经切除术也未消除MMC,但通过增加第2相的持续时间降低了频率。利血平处理(2.5mg/kg皮下注射)比6-OHDA处理更大程度地降低了MMC的频率。对去神经、6-OHDA处理和利血平处理动物的组织进行组织化学和免疫组织化学评估证实,手术去神经消除了胃和小肠的感觉神经和肾上腺素能神经,而化学性交感神经切除术仅影响肾上腺素能神经元。利血平处理使外在肾上腺素能神经元中的去甲肾上腺素耗竭,也使内在肠道神经元中的5-羟色胺耗竭。在豚鼠中,十二指肠第3相期间胃窦肌电活动会短暂受到抑制。在手术去神经的动物、6-OHDA处理的动物以及急性用胍乙啶处理的动物中,十二指肠第3相期间胃抑制持续存在。这些结果表明,豚鼠小肠中MMC的起始和传播不需要外在感觉神经和交感神经。(摘要截断于400字)

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