Advenier C, Devillier P, Blanc M, Gnassounou J P
Department of Pharmacology, Faculty of Medicine, Paris, France.
Pulm Pharmacol. 1990;3(3):137-44. doi: 10.1016/0952-0600(90)90044-j.
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) greater than Ro5-4864 (pKi = 5.43 +/- 0.18, n = 6) greater than or equal to diazepam greater than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
据报道，双嘧达莫（一种腺苷摄取抑制剂）和一些苯二氮䓬类药物可增强外周器官对腺苷的反应，尤其是对豚鼠离体心房的反应。在本文中，我们研究了双嘧达莫、地西泮以及四种对中枢（氯硝西泮）或外周（Ro5-4864）型苯二氮䓬受体具有选择性激动活性或对中枢（氟马西尼）或外周（PK 11195）苯二氮䓬受体具有拮抗活性的化合物在体外对豚鼠气管中腺苷反应的增强作用。在基础张力且无腺苷的制剂中，双嘧达莫（10⁻⁵ M）和除氟马西尼外的苯二氮䓬类药物（10⁻⁴ M）可引起气道平滑肌松弛。此外，地西泮（10⁻⁴ M）可减弱对组胺（10⁻⁵ M）的相位反应。双嘧达莫以及苯二氮䓬类激动剂地西泮、Ro5-4864和氯硝西泮（10⁻⁵至10⁻⁴ M）可增强气管对腺苷的反应，效力顺序为双嘧达莫（pKi = 7.77 ± 0.12，n = 8）大于Ro5-4864（pKi = 5.43 ± 0.18，n = 6）大于或等于地西泮大于氯硝西泮（pKi = 4.84 ± 0.11，n = 6）。两种苯二氮䓬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）存在的情况下，地西泮（10⁻⁴ M）对腺苷不会引起进一步增强作用。此外，地西泮产生的增强作用未被氟马西尼拮抗，而被PK 11195强烈拮抗。同样，PK 11195强烈抑制Ro5-4所产生的腺苷增强作用。（摘要截断于250字） 4864产生的腺苷增强作用。（摘要截断于250字）
