Church M K, Young K D
Br J Pharmacol. 1983 Apr;78(4):671-9. doi: 10.1111/j.1476-5381.1983.tb09419.x.
1 Three drugs have been tested for activity against antigen-induced histamine release from passively sensitized human lung fragments after increasing periods of pre-incubation before challenge.2 After 30 s pre-incubation, sodium cromoglycate inhibited histamine release in the concentration range 0.2-200 muM, producing a maximum inhibition of 33.0%. As the pretreatment period was extended, tolerance developed in a dose-related manner, resulting in a 48.3% and 82.8% loss of activity of the 200 muM dose after 60 min and 19 h pre-incubation, respectively. Tolerance was independent of extracellular calcium and was poorly reversible. Lung tissue desensitized to cromoglycate was cross-tolerant to the related drug, bufrolin, but not to salbutamol or chlorpromazine.3 In acute studies, salbutamol (0.03-3.0 muM) produced dose-related inhibition of histamine release, with a maximum inhibition of 72.2%. The effect was blocked stereoselectively by 1 muM propranolol, suggesting that it occurred through an interaction with lung beta-adrenoceptors. Increasing the pre-incubation time with salbutamol from 30 s to 19 h did not produce tolerance. Inhibition produced by incubation with salbutamol for 19 h was totally prevented when propranolol was added at the beginning of the pre-incubation period, indicating that it resulted from stimulation of beta-receptors and not from a non-specific or toxic effect. However, studies of reversibility of effect through washing or late addition of propranolol did indicate some change in the nature of salbutamol inhibition with time.4 Chlorpromazine was a weak inhibitor of immunological histamine release. A 100 muM concentration was ineffective after 30 s pre-incubation but its activity increased with time. Pre-incubation of lung fragments with this concentration for 1 h or longer, or with a 1 mM dose for a shorter period, provoked histamine release in the absence of antigen. Effects of chlorpromazine were not reversed by washing.5 The different characteristics shown by sodium cromoglycate, salbutamol and chlorpromazine indicate that these drugs inhibit histamine release by interfering with the secretory mechanisms in different ways.
三种药物在激发前经过不同时长的预孵育后，针对抗原诱导的被动致敏人肺组织片段中组胺释放的活性进行了测试。
预孵育30秒后，色甘酸钠在0.2 - 200μM浓度范围内抑制组胺释放，最大抑制率为33.0%。随着预处理时间延长，耐受性呈剂量相关方式发展，预孵育60分钟和19小时后，200μM剂量的活性分别损失48.3%和82.8%。耐受性与细胞外钙无关且难以逆转。对色甘酸钠脱敏的肺组织对相关药物布福林产生交叉耐受性，但对沙丁胺醇或氯丙嗪不产生交叉耐受性。
在急性研究中，沙丁胺醇（0.03 - 3.0μM）产生剂量相关的组胺释放抑制作用，最大抑制率为72.2%。该作用被1μM普萘洛尔立体选择性阻断，表明其通过与肺β - 肾上腺素能受体相互作用发生。将沙丁胺醇的预孵育时间从30秒增加到19小时未产生耐受性。预孵育开始时加入普萘洛尔可完全阻止沙丁胺醇孵育19小时所产生的抑制作用，表明这是由β - 受体刺激引起的，而非非特异性或毒性作用。然而，通过洗涤或后期加入普萘洛尔对作用可逆性的研究确实表明，沙丁胺醇抑制的性质随时间有所变化。
氯丙嗪是免疫性组胺释放的弱抑制剂。预孵育30秒后，100μM浓度无效，但其活性随时间增加。用该浓度对肺组织片段预孵育1小时或更长时间，或用1mM剂量预孵育较短时间，在无抗原时会引发组胺释放。氯丙嗪的作用不能通过洗涤逆转。
色甘酸钠、沙丁胺醇和氯丙嗪表现出的不同特性表明，这些药物通过不同方式干扰分泌机制来抑制组胺释放。
