组胺H3受体对垂体瘤AtT-20细胞分泌ACTH的调节作用

目的　观察组胺受体激动剂对AtT-20细胞分泌ACTH的影响，并探讨G蛋 白在组胺H3 受体信号转导机制中的作用. 方法　选用文献报道的高表达组胺H3受体 的垂体细胞瘤AtT-20 作为观察系统，用放免分析法测定给予组胺受体激动剂后各时间点细胞上清液中ACTH分泌量 的变化，并观察药物对细胞增殖的影响. 结果　组胺H3受体激动剂R- (α)- MeHA（0.1 μmol*L-1）作用8 h能明显促进ACTH的释放，释放量为1920 μg * L-1，与同时间对照组（780 μg*L-1）相比，明显增高（P<0.01）；H 1和H2激动剂则无此作用. 且R-(α)-MeHA引起ACTH分泌 的效应能被H3受体特异性拮抗剂thioperamide所拮抗，而H1受体和H2受体拮抗剂均不 影响 R-(α)-MeHA的效应. R-(α)-MeHA作用8和24h，对细胞增殖无明显影响. 用G蛋白失活 剂NEM 预先处理细胞后，取消了R-(α)-MeHA增强AtT-20细胞ACTH分泌的效应. 结论 　特异性激动组胺H3受体后能引起兴奋-分泌耦联过程，其信号转导过程中有G蛋白的参与.

Histamine H3 receptors regulate ACTH release by AtT-20 cel ls

AIM　To investigate the signal transduction mechanism of histamine H3 r eceptor. METHODS　The adrenocorticotropic hormone (ACTH) levels of supernatants on AtT- 20 cells from the pituitary gland tumor were measured by radioimmunoassa y at the given time after histamine agonists were administrated and the effects o f R-(α)-methylhistamine on the cells proliferation were observed. RES ULTS　The H3 receptor specific agonist, R-(α)-methylhistamine incre ased the release of A CT H in time-dependent manner. It increased significantly after administrated r e agents 8 h which reached 1920 μg*L-1 compared to the control group 7 80 μg*L-1 . while the H1 receptor agonist 2-methylhistamine and the H2 agonist impro midine were significantly less potent. Furthermore, this response was blocked by thiop eramide, an H3 receptor specific antagonist, but not by the H1 and H2 anta gonist chlorpheniramine and cimetidine. R-(α)- methylhistamine had no significant i nf luence on cell proliferation within 24 h. Pretreatment with N-ethylmaleimide (N EM ) could abolish the effects of R-(α)-methylhistamine on the release of ACTH. CO NCLUSION　Specific activation of H3 receptor could evoke the excitatio n-secreti on coupling process, and G protein might be involved in the signal transdu ction.