De Mendonça A, Ribeiro J A
Laboratory of Pharmacology, Gulbenkian Institute of Science, Oeiras, Portugal.
Eur J Pharmacol. 1989 May 19;164(2):347-54. doi: 10.1016/0014-2999(89)90476-7.
The effect of diazepam and its interaction with adenosine on evoked endplate potentials (e.p.p.s) and on twitch tension were investigated in innervated sartorius muscles of the frog. Diazepam (100 microM) reversibly decreased the amplitude of the e.p.p.s and the twitch responses evoked by indirect stimulation, and reversibly increased the resting membrane potential recorded from the endplates. In a concentration (30 microM) virtually devoid of an effect on the e.p.p.s, twitch responses, or resting membrane potential of the muscle fibres, diazepam potentiated the inhibitory action of adenosine on neuromuscular transmission, but not that induced by the stable analogue of adenosine 5'-N-ethylcarboxamide adenosine (NECA), which is not a substrate for the adenosine uptake system. The potentiating effect of diazepam was not observed in the presence of dipyridamole, an adenosine uptake blocker which potentiated the effect of adenosine on neuromuscular transmission. Diazepam shifted to the left the concentration-response curve obtained for adenosine in the presence of the adenosine receptor antagonist 8-phenyltheophylline (8-PT). The results suggest that diazepam acts at the frog neuromuscular junction by increasing the level of adenosine at the junction level; this increase probably results from inhibition in the uptake of the nucleoside.
在青蛙的受神经支配的缝匠肌中，研究了地西泮及其与腺苷对诱发终板电位（e.p.p.s）和抽搐张力的影响。地西泮（100微摩尔）可逆地降低了间接刺激诱发的e.p.p.s的幅度和抽搐反应，并可逆地增加了终板记录的静息膜电位。在对肌肉纤维的e.p.p.s、抽搐反应或静息膜电位几乎没有影响的浓度（30微摩尔）下，地西泮增强了腺苷对神经肌肉传递的抑制作用，但对腺苷5'-N-乙基羧酰胺腺苷（NECA）的稳定类似物诱导的抑制作用没有增强，NECA不是腺苷摄取系统的底物。在存在双嘧达莫（一种腺苷摄取阻滞剂，其增强了腺苷对神经肌肉传递的作用）的情况下，未观察到地西泮的增强作用。在存在腺苷受体拮抗剂8-苯基茶碱（8-PT）的情况下，地西泮使腺苷的浓度-反应曲线向左移动。结果表明，地西泮通过增加神经肌肉接头处的腺苷水平而作用于青蛙神经肌肉接头；这种增加可能是由于核苷摄取的抑制所致。
