阿托品和格隆溴铵对大鼠膈神经-膈肌标本神经肌肉传递的影响。

Effects of atropine and glycopyrrolate on neuromuscular transmission in the rat phrenic nerve-diaphragm preparation.

作者信息

Wali F A, Suer A H, McAteer E, Dark C H, Jones C J

机构信息

Anaesthetics Unit, London Hospital Medical College, Whitechapel, England.

出版信息

Gen Pharmacol. 1988;19(2):285-90. doi: 10.1016/0306-3623(88)90078-x.

DOI:10.1016/0306-3623(88)90078-x

PMID:2832247

Abstract

The effects of atropine and glycopyrrolate on neuromuscular transmission and on muscle contraction, were studied, in the rat diaphragm preparation, by analyzing their effects on the indirectly (and directly)-elicited twitch (0.2 Hz), tetanic (50 Hz for 20 sec duration), post-tetanic twitch responses (at 5 sec after the tetanus), and on the phenomenon of post-tetanic twitch potentiation (PTP), which is thought to be of a presynaptic origin, i.e. due to increased transmitter release. 2. Atropine (0.001-10 microM) increased the indirectly-elicited twitch tension by 22 +/- 2.1% (control 0.9 +/- 0.1 g, P less than 0.02), the tetanus by 15 +/- 1.1% (control 3.9 +/- 0.7 g, P less than 0.05), the post-tetanic twitch response by 33 +/- 3.1% (control 1.2 +/- 0.1 g, P less than 0.01) and the PTP value by 36 +/- 1.9% (control 33 +/- 2.3%, P less than 0.01, means +/- SEM = 6). 3. Atropine (0.001-10 microM) had little effect on the directly-elicited twitch tension, but in high concentrations (e.g. 20 microM), it blocked the twitch tension. 4. In contrast, glycopyrrolate (0.1-100 microM) had little effect on the twitch tension (direct or indirect), but it significantly reduced the tetanus (by 38 +/- 3.5%, P less than 0.01), the post-tetanic twitch response (by 17 +/- 1.2%, P less than 0.05) and the PTP values (by 24 +/- 3.1% P less than 0.02). 5. In the presence of hemicholinium (1.3 microM) the responses to atropine and glycopyrrolate were altered (decreased), indicating a possible action on presynaptic mechanism of transmission. 6. It is concluded that atropine and glycopyrrolate produce different (opposite) effects at the rat neuromuscular junction, atropine enhances whereas glycopyrrolate depresses neuromuscular transmission. The effects of these two antimuscarinic drugs may be exerted at the presynaptic nerve terminals, i.e. on presynaptic muscarinic receptors, which are involved in the feedback mechanism of transmitter release.

摘要

通过分析阿托品和格隆溴铵对大鼠膈神经膈肌标本中间接（和直接）诱发的抽搐（0.2Hz）、强直收缩（50Hz，持续20秒）、强直后抽搐反应（强直收缩后5秒）以及强直后抽搐增强现象（PTP）的影响，研究了它们对神经肌肉传递和肌肉收缩的作用。PTP被认为源于突触前，即由于递质释放增加。2. 阿托品（0.001 - 10μM）使间接诱发的抽搐张力增加22±2.1%（对照组0.9±0.1g，P＜0.02），强直收缩增加15±1.1%（对照组3.9±0.7g，P＜0.05），强直后抽搐反应增加33±3.1%（对照组1.2±0.1g，P＜0.01），PTP值增加36±1.9%（对照组33±2.3%，P＜0.01，均值±标准误，n = 6）。3. 阿托品（0.001 - 10μM）对直接诱发的抽搐张力影响很小，但在高浓度（如20μM）时，它会阻断抽搐张力。4. 相比之下，格隆溴铵（0.1 - 100μM）对抽搐张力（直接或间接）影响很小，但它显著降低了强直收缩（降低38±3.5%，P＜0.01）、强直后抽搐反应（降低17±1.2%，P＜0.05）和PTP值（降低24±3.1%，P＜0.02）。5. 在存在半胱氨酸（1.3μM）的情况下，对阿托品和格隆溴铵的反应发生改变（降低），表明它们可能对突触前传递机制有作用。6. 得出的结论是，阿托品和格隆溴铵在大鼠神经肌肉接头处产生不同（相反）的作用，阿托品增强而格隆溴铵抑制神经肌肉传递。这两种抗毒蕈碱药物的作用可能是在突触前神经末梢，即作用于参与递质释放反馈机制的突触前毒蕈碱受体。