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.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006918:Hydroxyurea / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008761:Methylhistamines / Q000494:pharmacology; D008785:Metiamide / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D011968:Receptors, Histamine / Q000502:physiology*; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000502:physiology*
D007093:Imidazoles; D008761:Methylhistamines; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D008785:Metiamide; D002738:Chloroquine; D004247:DNA; D006918:Hydroxyurea