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二甲基亚砜的心脏变时机制:对乙酰胆碱酯酶的抑制作用以及阿托品对负性变时作用的拮抗作用。

Cardiac chronotropic mechanisms of dimethyl sulphoxide: inhibition of acetylcholinesterase and antagonism of negative chronotropy by atropine.

作者信息

Shlafer M, Matheny J L, Karow A M

出版信息

Arch Int Pharmacodyn Ther. 1976 May;221(1):21-31.

PMID:962427
Abstract

The chronotropic effects of dimethyl sulphoxide (DMSO) were studied in spontaneously beating rabbit atria. Low concentrations of DMSO (0.14, 0.42 M) produced slight positive chronotropic (+C) responses; 0.84 and 1.41 M DMSO caused significant negative chronotropic (--C) responses. All concentrations decreased contractile strength. Atropine sulphate (10)-7) to 10(-5) M) antagonized the chronotropic effects, but not the inotropic effects. In the presence of atropine all DMSO concentrations produced significant +C responses. Reserpine pretreatment or propranolol did not affect contractile responses to DMSO in the absence or presence of atropine. DMSO produced concentration-dependent inhibition of acetylcholinesterase (AChE) activity of atrial homogenates. The results indicate that the --C responses are due specifically to AChE inhibition by DMSO and resulting cholinergic influences on the atrial pacemaker. Adrenergic mechanisms do not appear to mediate the +C responses. Data presented here provide evidence that a cardioactive effect of DMSO is mediated by a well-defined receptor-linked mechanism, and that this effect can be modified by a specific receptor blocking agent.

摘要

在自发性搏动的兔心房中研究了二甲基亚砜(DMSO)的变时作用。低浓度的DMSO(0.14、0.42 M)产生轻微的正性变时(+C)反应;0.84和1.41 M的DMSO引起显著的负性变时(-C)反应。所有浓度均降低收缩强度。硫酸阿托品(10^-7至10^-5 M)拮抗变时作用,但不拮抗变力作用。在阿托品存在的情况下,所有DMSO浓度均产生显著的+C反应。利血平预处理或普萘洛尔在有无阿托品的情况下均不影响对DMSO的收缩反应。DMSO对心房匀浆的乙酰胆碱酯酶(AChE)活性产生浓度依赖性抑制。结果表明,-C反应是由于DMSO对AChE的特异性抑制以及由此产生的胆碱能对心房起搏器的影响。肾上腺素能机制似乎不介导+C反应。此处提供的数据表明,DMSO的心脏活性作用是由明确的受体连接机制介导的,并且这种作用可以被特定的受体阻断剂改变。

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