PERIPHERAL TYPE BENZODIAZEPINE RECEPTORS AND RESPONSE TO ADENOSINE ON THE GUINEA-PIG ISOLATED TRACHEA
PERIPHERAL TYPE BENZODIAZEPINE RECEPTORS AND RESPONSE TO ADENOSINE ON THE GUINEA-PIG ISOLATED TRACHEA
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DOI：
10.1016/0952-0600(90)90044-j
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发表时间：
1990-01-01
期刊：
影响因子：
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通讯作者：
GNASSOUNOU J P
中科院分区：
文献类型：
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作者：
ADVENIER C;DEVILLIER P;GNASSOUNOU J P
据报道，双嘧达莫，腺苷摄取抑制剂，和一些苯二氮卓类药物加强周围器官，特别是豚鼠离体心房的腺苷的反应。在本文中，我们已经研究了增强反应产生腺苷双嘧达莫，地西泮和四个化合物的选择性激动活性对中央（氯硝西泮）或外周（Ro 5 -4864）型苯二氮受体或拮抗活性对中央（氟马西尼）或外周（PK 11195）苯二氮受体在豚鼠离体气管。在基础张力和腺苷，双嘧达莫（10-5 M）和苯二氮卓类药物（10-4 M）的情况下，除氟马西尼诱导的气道平滑肌松弛的准备工作。此外，地西泮（10-4 M）衰减组胺（10-5 M）的阶段性反应。双嘧达莫和苯二氮激动剂地西泮、Ro 5 -4864和氯硝西泮（10-5至10-4 M）产生增强气管对腺苷的反应，效力的等级顺序为双嘧达莫（pKi = 7.77 ± 0.001）。0.12，n = 8）> Ro5-4864（pKi = 5.43 . ±. 0.18，n = 6）≥地西泮>氯硝西泮（pKi = 4.84 ±. 0.11，n = 6）。两种苯二氮卓类受体拮抗剂氟马西尼和PK 11195仅在10-4 M时对腺苷产生显著但较小的增强作用。在双嘧达莫（10-5 M）的存在下，地西泮（10-4 M）没有引起任何进一步的增强腺苷。 此外，地西泮产生的增效作用未被氟马西尼拮抗，而PK 11195则有效拮抗。同样，PK 11195可有效抑制Ro 5 -4864产生的腺苷增强作用。在双嘧达莫的存在下，腺苷和茶碱之间的拮抗作用似乎是竞争型的，而不是在地西泮的存在下或在没有双嘧达莫的情况下。机械去除气管上皮显着增强豚鼠气管腺苷松弛，但并没有改变双嘧达莫或地西泮的效果。因此，苯二氮卓类药物似乎通过抑制腺苷摄取而增强豚鼠气管对腺苷的反应，这可能是通过激活外周型苯二氮卓受体而发生的。
It has been reported that dipyridamole, an adenosine uptake inhibitor, and some benzodiazepines potentiate the responses to adenosine in peripheral organs and in particular, on guinea-pig isolated atria. In this paper, we have examined the potentiation of responses to adenosine produced by dipyridamole, diazepam and four compounds with selective agonistic activity towards the central (clonazepam) or peripheral (Ro5-4864) type benzodiazepine receptors or antagonistic activity towards the central (flumazenil) or peripheral (PK 11195) benzodiazepine receptors in guinea-pig trachea in vitro. In preparations under basal tone and in the absence of adenosine, dipyridamole (10-5 M) and benzodiazepines (10-4 M) with the exception of flumazenil induced a relaxation of the airway smooth muscle. In addition, diazepam (10-4 M) attenuated the phasic response to histamine (10-5 M). Dipyridamole, and the benzodiazepine agonists diazepam, Ro5-4864 and clonazepam (10-5 to 10-4 M) produced potentiation of the tracheal response to adenosine, the rank order of potency being dipyridamole (pKi = 7.77 .+-. 0.12, n = 8) > Ro5-4864 (pKi = 5.43 .+-. 0.18, n = 6) .gtoreq. diazepam > clonazepam (pKi = 4.84 .+-. 0.11, n = 6). The two benzodiazepine receptor antagonists, flumazenil and PK 11195, gave a significant but small potentiation to adenosine only at 10-4 M. In the presence of dipyridamole (10-5 M), diazepam (10-4 M) did not cause any further potentiation to adenosine. Additionally, the potentiation produced by diazepam was not antagonised by flumazenil, whereas it was potently antagonised by PK 11195. Similarly, PK 11195 potently inhibited the adenosine potentiation produced by Ro5-4864. In the presence of dipyridamole, the antagonism between adenosine and theophylline appeared to be of the competitive type whereas it did not in the presence of diazepam or in the absence of dipyridamole. Mechanical removal of the tracheal epithelium significantly potentiated the relaxation of guinea-pig trachea to adenosine but did not alter the effect of dipyridamole or diazepam. Benzodiazepines therefore appear to potentiate the response of guinea-pig trachea to adenosine by inhibition of adenosine uptake, and this might occur through activation of a peripheral type benzodiazepine receptor.