氨甲酰胆碱和Impromidine对CFU—S细胞周期的影响

正常情况下处于S期的CFU-S比例低于10％。氨甲酰胆碱(Cach 10~(-13)—10~(-9)mol/L)和Impromidine(Impro 10~(-9)—10~(-4)mol/L)在体外与小鼠骨髓细胞短时培育后,增加了CFU-S对细胞毒剂羟基脲的敏感性。反应最大时,9d和13dCFU-S的减少率分别是32.8和60.6％(Cach)以及38.4和49.5％(Impro)。这种效应可分别被胆碱能N受体阻断剂筒箭毒(10~(-6)mol/L)和组胺H_2受体阻断剂甲氰咪呱(10~(-6)mol/L)所阻断,表明9d和13d CFU-S表面胆碱能N受体和组胺H_2受体的密度或活性存在差别,再次证实了CFU-S是一个不均一的细胞群。

EFFECTS OF CARBAMYLCHOLINE AND IMPROMIDINE ON CELL CYCLE STATE OF CFU-S

In normal steady-state conditions, there was less than 10% loss of CFU-S due to hydroxyurea (HU, 10(-3) mol/L). The CFU-S killed by HU was greatly increased after bone marrow cells of LACA mice were exposed in vitro to carbamylcholine (Cach) (10(-13)-10(-9) mol/L) and impromidine (Impro) (10(-9)-10(-4) mol/L). They were 32.8 (Cach) and 38.4% (Impro) for day 9 CFU-S; 60.6 (Cach) and 49.5% (Impro) for day 13 CFU-S at plateau phase. The effects were blocked by antagonists of cholinergic N receptor d-tubocurarine and of histamine H2 receptor cimetidine, respectively. The different sensitivity to agonists between CFU-S forming early spleen colonies and late colonies may reflect differences in receptor density on the surface of haemopoietic stem cells or receptor activity. The studies provide additional evidence suggesting the heterogeneity of pluripotent haemopoietic stem cells.