组胺H_2-受体激动剂和H_1-受体激动剂对多能造血干细胞(CFU-S)细胞周期影响的拮抗作用

本实验显示组胺H_2受体激动剂4-甲基组胺可促使更多的多能造血干细胞进入细胞周期,而组胺H_1受体激动剂2-甲基组胺则能拮抗4-甲基组胺的这一作用。4-甲基组胺与2-甲基组胺对造血干细胞周期状态的影响之间又呈现相互竞争现象。文中讨论了上述实验事实的理论意义。

THE ANTAGONISTIC EFFECT OF HISTAMINE H_2-RECEPTOR AGONIST AND H_1- RECEPTOR AGONIST ON THE CELL CYCLE RESPONSE OF HEMATOPOIETIC CELLS

It was shown that the treatment of mouse bone marrow cells with 4-methylhistamine (an H2-receptor agonist) triggered the hematopoietic stem cells (CFU-S) from the G0 state into the S-phase of the cell-cycle, while 2-methylhistamine (an H1-receptor agonist) showed no such effect. In order to explore the cellular mechanism of the cell-cycle effect of 4-methylhistamine on CFU-S, the mutual influence between 4-methylhistamine and 2-methylhistamine was investigated. In this experiment the bone marrow cells of BDF female mice were first treated with histamine derivatives for one hour then exposed to hydroxyurea (HU, 10-3M) for another hour. These cells finally were injected intravenously into syngenic irradiated mice (820 rad), spleen colonies were counted 9 days later. The percent loss of CFU-S was calculated. The result showed that for the bone marrow cells treated with 4-methylhistamine (10-8M) alone there was 30-50% loss of CFU-S due to HU, while for the bone marrow cells treated with 4-methylhistamine (10-8 M) and 2-methylhistamine (10-8M) together the CFU-S loss due to HU was only 6-18%.The antagonistic effect of 2-methylhistamine could be reversed by higher concentration of 4-methylhistamine (10-7M). These findings suggest that H2-receptor agonist and H1-receptor agonist have an antagonistic effect on the cell-cycle response of CFU-S. A further study of the role of H1- and H2- receptors in the regulation of cell-cycle changes appears to be significant.