A ganglionic stimulant, 1,1-dimethyl-4-phenylpiperazinium, caused both cholinergic and adrenergic responses in the isolated mouse atrium
A ganglionic stimulant, 1,1-dimethyl-4-phenylpiperazinium, caused both cholinergic and adrenergic responses in the isolated mouse atrium
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神经节兴奋剂 1,1-二甲基-4-苯基哌嗪鎓在离体小鼠心房中引起胆碱能和肾上腺素能反应
DOI：
10.1016/j.ejphar.2013.02.019
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
T
中科院分区：
文献类型：
--
作者：
Ochi;K.;Teraoka;H.;Unno;T.;Komori;S.;Yamada;M.;Kitazawa;T
离体小鼠心房标本可用于分析药物对心肌、自主神经元和内皮细胞的作用。本研究的目的是用神经节兴奋剂1，1-二甲基-4-苯基哌嗪（DMPP）研究心房内神经元的功能。DMPP（1-100μM）在自发搏动的右心房中引起负性变时作用，随后是正性变时作用，还引起双相变力作用，包括电场刺激（EFS）诱导的左心房收缩的初始抑制，随后是增强。用M2和/或M3受体基因敲除小鼠（M2 R-KO、M3 R-KO和M2M 3R-KO）和某些植物药观察DMPP对左心房的变力作用。阿托品和六甲双铵可减弱DMPP的初始负性肌力作用。在百日咳毒素处理的M2 R-KO和M2/M3 R-KO小鼠的心房中，负性肌力作用被消除。另一方面，以下正性肌力作用被六甲双铵、阿托品和阿替洛尔减弱。在利血平处理的小鼠心房中，正性肌力作用也降低。DMPP诱导的正性肌力作用在M2 R-KO小鼠中几乎相同，但在M3 R-KO小鼠和M2/M3 R-KO小鼠中均降低。总之，DMPP通过激活内源性胆碱能和肾上腺素能神经元引起小鼠心房的双相变力/变时作用。M2和M3受体及β1肾上腺素受体参与了上述作用。
An isolated atrial preparation of the mouse is useful for analyzing the actions of drugs on the myocardium, autonomic neurons and endocardial endothelium. The aim of the present study was to examine the functions of intrinsic neurons of the atrium using a ganglionic stimulant, 1,1-dimethyl-4-phenylpiperazinium (DMPP). DMPP (1–100μM) caused a negative chronotropic action followed by a positive chronotropic action in spontaneously beating right atria and also caused biphasic inotropic actions consisting of initial inhibition followed by potentiation of electrical field stimulation (EFS)-induced contraction in the left atria. Inotropic actions in the left atria induced by DMPP were characterized using some autonomic drugs and M2and/or M3muscarinic receptor knockout (M2R-KO, M3R-KO and M2M3R-KO) mice. Atropine and hexamethonium decreased the initial negative inotropic actions of DMPP. In the atria from pertussis toxin-treated, M2R-KO and M2/M3R-KO mice, the negative inotropic actions were abolished. On the other hand, the following positive inotropic actions were decreased by hexamethonium, atropine and atenolol. In the atria from reserpine-treated mice, positive inotropic actions were also decreased. The positive inotropic action induced by DMPP was almost the same in M2R-KO mice but was reduced in both M3R-KO mice and M2/M3R-KO mice. In conclusion, DMPP caused biphasic inotropic/chronotropic actions in the mouse atrium through activation of intrinsic cholinergic and adrenergic neurons. M2and M3muscarinic receptors and β1-adrenoceptor are thought to be involved in these actions.