A re-appraisal of the nature of the atropine-resistant contraction to electrical field stimulation in the human isolated detrusor muscle
A re-appraisal of the nature of the atropine-resistant contraction to electrical field stimulation in the human isolated detrusor muscle
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人离体逼尿肌对电场刺激的阿托品抵抗性收缩性质的重新评价
DOI：
10.1007/pl00005114
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发表时间：
1997
期刊：
影响因子：
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通讯作者：
M. Tonini
中科院分区：
文献类型：
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作者：
M. Tagliani;S. Candura;A. Di Nucci;G. Franceschetti;G. D'agostino;P. Ricotti;E. Fiori;M. Tonini
摘要：我们研究了人类离体逼尿肌对电场刺激的抗阿托品收缩反应是否由ATP（或相关嘌呤）介导，正如之前在其他哺乳动物的膀胱中所显示的那样。电刺激（1-50Hz，间隔1min， 0.1ms脉宽，60V，持续5s）引起可重复的、频率相关的抽搐收缩，阿托品（10μM）显著降低了这种收缩。河豚毒素（TTX: 1μM）对收缩反应的抑制程度相似。当一起使用时，阿托品和TTX引起的抑制作用与单独使用任何一种药物引起的抑制作用重叠。ω- concontoxin GVIA （ω-CTX: 0.1μM）对抗ttx收缩完全没有影响。p2 -嘌呤受体拮抗剂苏拉明（300μM）和PPADS （30μM）在抑制ATP （10μM-1mM）诱导的收缩反应时，对阿托品耐药的收缩反应没有影响。如前所述，苏拉明（30、100、300μM）和PPADS（3、10、30μ m）对atp诱导的收缩的拮抗作用是不可克服的，其表观“pA2”值（以最低拮抗剂浓度计算）分别为4.9和5.2。结论是，在我们的实验条件下，尽管效应细胞上存在兴奋性p2 -嘌呤受体，但人类逼尿肌兴奋性传递的非胆碱能（抗阿托品）成分不是由ATP的神经释放介导的。抗TTX和ω- ctx的非胆碱能成分可能与通过独立于Na+和n型Ca2+通道的机制释放未知递质有关。更有可能的是，抗阿托品成分可能反映了平滑肌的直接兴奋，因为人类逼尿肌的时间非常短（Sibley 1984）。
Abstract We investigated whether in human isolated detrusor strips the atropine-resistant contractile response to electrical field stimulation was mediated by ATP (or a related purine), as previously shown in the urinary bladder of other mammalian species. Electrical stimulation (1–50Hz for 5s at 1min intervals, 0.1ms pulse width, 60V) elicited reproducible, frequency-dependent twitch contractions, which were markedly reduced by atropine (10μM). Tetrodotoxin (TTX: 1μM) inhibited contractile responses to a similar degree. When applied together, atropine and TTX caused an inhibition which was superimposable to that caused by either drug alone. The TTX-resistant contractions were totally unaffected by omega-conotoxin GVIA (ω-CTX: 0.1μM). The atropine-resistant contractions were unaffected by the P2-purinoceptor antagonists suramin (300μM) and PPADS (30μM), at concentrations which virtually suppressed the contractile response induced by applied ATP (10μM–1mM). As previously described, antagonism of the ATP-induced contractions by suramin (30, 100, 300μM) and PPADS (3, 10, 30μM) was insurmountable, with apparent ‘pA2’ values (calculated at the lowest antagonist concentrations) of 4.9 and 5.2, respectively. It is concluded that, under our experimental conditions, the non-cholinergic (atropine-resistant) component of the excitatory transmission in the human detrusor is not mediated by neural release of ATP, in spite of the presence of excitatory P2-purinoceptors on the effector cells. The TTX- and ω-CTX-resistant, non-cholinergic component might be related to the release of unknown transmitter(s) through a mechanism independent of both Na+- and N-type Ca2+-channels. More likely, the atropine-resistant component may reflect direct smooth muscle excitation since the human detrusor has a very short chronaxie (Sibley 1984).