地西泮作为腺苷增强剂的可能作用机制。

Possible mechanism of action of diazepam as an adenosine potentiator.

作者信息

Moritoki H, Fukuda H, Kotani M, Ueyama T, Ishida Y, Takei M

出版信息

Eur J Pharmacol. 1985 Jul 11;113(1):89-98. doi: 10.1016/0014-2999(85)90346-2.

Abstract

Diazepam (10(-5)-3 X 10(-4) M) selectively enhanced the negative inotropic responses of guinea-pig atria and the relaxation of guinea-pig taenia coli caused by adenosine and ATP. In the atria, the effect of 2-chloroadenosine, a stable analog of adenosine, was not affected by diazepam. Segments of guinea-pig atria or taenia coli took up 3H-activity during incubation with [3H]adenosine but did not take up 32P-activity from [32P]ATP. Diazepam at concentrations sufficient to enhance the in vitro responses reduced by half the uptake of 3H-activity into the preparations. Adenosine (10(-6) M) and ATP (10(-6) M) were degraded to inactive inosine during incubation with atrial segments and their degradation was inhibited by diazepam. In contrast, in rat atria, diazepam did not enhance the negative inotropic effects of adenosine and ATP, and did not prevent the uptake of adenosine. These results suggest that in guinea-pig atria and taenia coli, diazepam like dipyridamole, acts as an adenosine potentiator by preventing the uptake and degradation of adenosine.

摘要

地西泮（10⁻⁵ - 3×10⁻⁴ M）选择性增强豚鼠心房的负性肌力反应以及腺苷和ATP引起的豚鼠结肠带松弛。在心房中，腺苷的稳定类似物2-氯腺苷的作用不受地西泮影响。豚鼠心房或结肠带片段在与[³H]腺苷孵育期间摄取³H活性，但不摄取[³²P]ATP的³²P活性。足以增强体外反应的地西泮浓度使制剂中³H活性的摄取减少一半。腺苷（10⁻⁶ M）和ATP（10⁻⁶ M）在与心房片段孵育期间降解为无活性的肌苷，其降解受到地西泮抑制。相比之下，在大鼠心房中，地西泮不增强腺苷和ATP的负性肌力作用，也不阻止腺苷的摄取。这些结果表明，在豚鼠心房和结肠带中，地西泮与双嘧达莫一样，通过阻止腺苷的摄取和降解而作为腺苷增强剂起作用。