pyrimidinones and thioperamide

Murine hematopoietic progenitor cells synthesize substantial amounts of histamine in response to IL-3 or calcium ionophore. They also take up extracellular histamine by an active transport system. In the present study we demonstrate that this system mediates both influx and efflux of histamine. Indeed, MR16155 and thioperamide, the two H3 antagonists which are most effective in inhibiting histamine uptake, likewise diminish the release of preloaded histamine from bone marrow cells. These compounds also inhibit the release of histamine which has been newly synthesized by hematopoietic progenitors in response to IL-3 or calcium ionophore, as assessed by the accumulation of the mediator inside the cells in the presence of the antagonists. The potency of different histamine receptor antagonists as inhibitors of histamine release increases with their capacity to block histamine uptake.

Topics: Animals; Biological Transport; Calcium; Cell Line; Cetirizine; Cimetidine; Female; Hematopoietic Stem Cells; Histamine; Histamine Antagonists; Interleukin-3; Male; Mice; Mice, Inbred C57BL; Piperidines; Pyrimidinones; Sodium

Histamine, acting via H1 receptors, dose-dependently stimulated [3H]inositol phosphate production in GT1-7 neuronal cells. GT1-7 cells also responded to Substance P but not to other neuroactive drugs tested. Acute histamine pretreatment desensitised the histamine-induced response, resulting in a reduction in the maximal response and a slower time-course of [3H]-inositol phosphate production. The desensitisation phenomenon was reversible, with full recovery by 2 h.

Topics: Animals; Carbachol; Cell Line, Transformed; Dose-Response Relationship, Drug; Glutamic Acid; Histamine; Histamine Antagonists; Histamine H1 Antagonists; Hypothalamus; Inositol Phosphates; Kinetics; Mice; Neurons; Neuropeptide Y; Piperidines; Pyrimidinones; Ranitidine; Receptors, Histamine H1; Serotonin; Substance P; Tritium