Contractile and phosphatidylinositol responses of rat trachea to anticholinesterase drugs

Contractile and phosphatidylinositol responses of rat trachea to anticholinesterase drugs
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大鼠气管对抗胆碱酯酶药物的收缩和磷脂酰肌醇反应

DOI:
10.1007/bf03012462
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发表时间:
1998
期刊:
Canadian Journal of Anaesthesia
影响因子:
--
通讯作者:
K. Sumikawa
K. Sumikawa
中科院分区:
--
文献类型:
--
作者:
O. Shibata;A. Tsuda;T. Makita;Shunichiro Iwanaga;T. Hara;S. Shibata;K. Sumikawa

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目的:新斯的明、吡啶斯的明等抗胆碱酯酶(anti-ChE)能刺激磷脂酰肌醇(PI)反应。尽管PI反应的增加与气道平滑肌收缩之间存在直接关系,但没有关于抗ChE药物对气道平滑肌影响的数据。因此,我们研究了抗胆碱酯酶药物产生的收缩特性和PI反应。将大鼠气管环悬挂在Krebs-Henseleit(K-H)溶液中的两个不锈钢钩之间。(I)加入卡巴胆碱(CCh)、抗胆碱酯酶药物(新斯的明、吡啶斯的明、依洛酚铵)或DMPP(选择性神经节烟碱激动剂)诱导主动收缩。(2)本文观察了M_3受体拮抗剂4-二苯乙酰氧基-N-甲基哌啶甲溴化物(4-DAMP)对新斯的明或吡啶斯的明引起的大鼠气管环收缩的影响。(3)河豚毒素(TTX)对抗胆碱酯酶(ChE)药物诱导的反应。将气管切片置于含有LiCl和3 [H]肌醇的K-H溶液中,加入新斯的明或吡啶斯的明,并加入或不加入M3受体拮抗剂4-DAMP,用液体闪烁计数器计数3 [H]肌醇单磷酸(IP)的生成。结果卡巴胆碱(0.1 μM)、新斯的明(1 μM)、吡啶斯的明(10 μM)引起气管环收缩,而依洛酚铵和DMPP则不引起收缩。4-DAMP能抑制新斯的明和吡啶斯的明引起的收缩,而河豚毒素不能。4-DAMP.ConclusionsThe数据表明,抗胆碱酯酶药物激活气管效应部位的M3受体。
PurposeSome anticholinesterases (anti-ChE) such as neostigmine and pyridostigmine but not edrophonium, stimulate phosphatidylinositol (PI) response. Although a direct relationship was suggested between the increase in PI response and airway smooth muscle contraction, there are no data regarding the effects of anti-ChE drugs on airway smooth muscle. Thus, we examined the contractile properties and PI responses produced by anti-ChE drugs.MethodsContractile response. Rat tracheal ring was suspended between two stainless hooks in Krebs-Henseleit (K-H) solution. (I) Carbachol (CCh), anti-ChE drugs (neostigmine, pyridostigmine, edrophonium) or DMPP (a selective ganglionic nicotinic agonist) were added to induce active contraction. (2) The effects of 4-diphenylacetoxy-N-methyl-piperidine methobromide (4-DAMP), an M3muscarinic receptor antagonist, on neostigmineor pyridostigmine-induced contraction of rat tracheal ring were examined. (3) Tetrodotoxin (TTX) was tested on the anti-ChE drugs-induced responses.PI response. The tracheal slices were incubated in K-H solution containing LiCl and3[H]myo-inositol in the presence of neostigmine or pyridostigmine with or without 4-DAMP, an M3muscarinic receptor antagonist.3[H]inositol monophosphate (IP,) formed was counted with a liquid scintillation counter.ResultsCarbachol (0.1 μM), neostigmine (1 μM), pyridostigmine (10 μM) but not edrophonium or DMPP, caused tracheal ring contraction. 4-DAMP, but not tetrodotoxin, inhibited neostigmine and pyridostigmineinduced contraction. Neostigmineor pyridostigmine-induced IP1accumulation was inhibited by 4-DAMP.ConclusionsThe data suggest that anti-ChE drugs activate the M3receptors at the tracheal effector site.