Mechanism for histamine H2-receptor induced cell-cycle changes in the bone marrow stem cell.

The treatment in vitro of mouse bone marrow cells with 4-methylhistamine triggered the hematopoietic stem cell (CFU-S) from the G0 state into the S-phase of the cell cycle. In contrast, 2-methylhistamine had no such effect. Metiamide antagonized the effects of low concentrations of 4-methylhistamine. Antagonism by metiamide was reversed by high concentrations of 4-methylhistamine. Imidazole, and activator of phosphodiesterase, also suppressed the cell-cycle effects of 4-methylhistamine. The latter findings suggests that cyclic nucleotides may mediate in the stem cell response to 4-methylhistamine. Blocking the metabolism of endogenous histamine with a combination of aminoguanidine and chloroquine also initiated DNA synthesis in the bone marrow stem cell. Metiamide antagonized the effects of the aminoguanidine/chloroquine combination. These experiments associate a histamine H2-receptor with the hematopoietic stem cell. They also suggest that, if available, endogenous histamine can initiate cell-cycle changes in the pluripotent bone marrow stem cell.