Raeburn D, Miller L G, Summer W R
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans.
J Pharmacol Exp Ther. 1988 May;245(2):557-62.
It has been postulated that a benzodiazepine receptor with a micromolar affinity may be associated with Ca++ channels in peripheral organs. We examined the actions of Ro5-4684 (parachlorodiazepam) and midazolam on guinea pig tracheal smooth muscle contraction. Binding studies using [3H]Ro5-4684 indicate the presence of a "peripheral" type binding site with a Kd of approximately 4 nM and maximum binding of 1 pmol/mg of protein. Midazolam did not displace radioligand. In tension studies no activity was seen for Ro5-4684 or midazolam at concentrations below 1 microM. Higher concentrations relaxed the airway smooth muscle under basal tone, the effect was augmented significantly by epithelium removal. Similar results were obtained in tissues precontracted with methacholine or KCl. Midazolam (1 or 100 microM) significantly (P less than .05) attenuated the response to Ca++ in K+-depolarized tracheal strips, the effect was greater at low Ca++ concentrations. The compounds appear to function as Ca++ antagonists in airway smooth muscle but ar not typical as shown by their ability to reduce basal tone in airway smooth muscle.
据推测，一种具有微摩尔亲和力的苯二氮䓬受体可能与外周器官中的钙离子通道有关。我们研究了Ro5-4684（对氯安定）和咪达唑仑对豚鼠气管平滑肌收缩的作用。使用[3H]Ro5-4684进行的结合研究表明存在一种“外周”型结合位点，其解离常数约为4 nM，最大结合量为1 pmol/mg蛋白质。咪达唑仑不能取代放射性配体。在张力研究中，浓度低于1 microM时，未观察到Ro5-4684或咪达唑仑有活性。较高浓度可使基础张力下的气道平滑肌松弛，去除上皮后该作用显著增强。在用乙酰甲胆碱或氯化钾预收缩的组织中也得到了类似结果。咪达唑仑（1或100 microM）可显著（P<0.05）减弱钾离子去极化气管条对钙离子的反应，在低钙离子浓度时作用更强。这些化合物在气道平滑肌中似乎起钙离子拮抗剂的作用，但通过它们降低气道平滑肌基础张力的能力表明它们并不典型。
