thiourea and oxmetidine

This study investigated the effect of histamine generated by murine bone marrow cells in response to IL-3 on one particular biological activity of this growth factor, i.e., triggering of cells forming colonies in spleen (CFU-S) into S phase. Evidence is provided that i) IL-3-induced day-8 CFU-S cell cycling, evaluated by hydroxy-urea suicide, is completely abrogated when the binding of histamine to its H2 receptors is blocked by the specific antagonist oxmetidine, whereas cetirizine, a H1 receptor antagonist, is ineffective; and ii) the entry of day-8 CFU-S into S phase in response to IL-3 is likewise abolished when the histamine synthesis promoted by the growth factor is prevented by alpha-fluoromethylhistidine, a specific inhibitor of the histamine-forming enzyme, histidine decarboxylase. Similar results are obtained with both drugs, when a progenitor-enriched bone marrow population is used instead of total cells. Furthermore, i.v. injection of recombinant (r)IL-3 results within 2 hr in a substantial increase in bone marrow cell histamine synthesis together with triggering of day-8 CFU-S into cycle, the latter being completely abolished by a simultaneous injection of the H2 histamine receptor antagonist oxmetidine. Thus, our findings support the notion that both in vitro and in vivo the proliferation of early CFU-S in response to IL-3 is modulated by histamine via its H2 receptors. This conclusion is also consistent with the observation that dimaprit, a specific agonist of these receptors not only enhances the sensitivity of day-8 CFU-S to HU after a 2 hr incubation with bone marrow cells but also increases, to the same extent as IL-3, the number of colonies formed in irradiated spleens after a 5 hr pretreatment.

Topics: Animals; Bone Marrow Cells; Cell Division; Cetirizine; Colony-Forming Units Assay; Dimaprit; Hematopoiesis; Hematopoietic Stem Cells; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Hydroxyzine; Imidazoles; In Vitro Techniques; Interleukin-3; Methylhistidines; Mice; Mice, Inbred C57BL; Thiourea

Histamine H2-receptor antagonists cimetidine and oxmetidine, H2-receptor agonist dimaprit, H1-receptor antagonist chlorpheniramine and H1-receptor agonist 2-thiazolylethylamine were tested for their effects on unstimulated pancreatic exocrine secretion in anaesthetized rabbits fitted with an acute pancreatic cannula. Intravenous administration of H1 agonist induces a dose-dependent increase in pancreatic secretion but H1 antagonist have the opposite effects. Intravenous administration of H2 antagonists induces effects similar the ones produced after H1 agonist infusion. The implications of H1 and H2 receptors on exocrine pancreatic secretion are discussed.

Topics: Animals; Chlorpheniramine; Cimetidine; Dimaprit; Dose-Response Relationship, Drug; Female; Histamine H1 Antagonists; Histamine H2 Antagonists; Imidazoles; Kinetics; Male; Pancreas; Rabbits; Receptors, Histamine H1; Receptors, Histamine H2; Thiazoles; Thiourea

Distribution and properties of histamine H2-receptor mediated responses in segments of rabbit aorta was studied with histamine and H2-receptor stimulating drugs, dimaprit and impromidine. All agonists produced concentration-dependent tonus decreased in precontracted vascular strips, which were antagonised by selective H2-receptor antagonists, cimetidine and oxmetidine. Activities of the agonists were segment-dependent, and increased caudally along the aorta. A nonspecific smooth muscle relaxant, papaverine had homogeneous activity along the vessel, suggesting receptor specific nature of the observed heterogeneity.

Topics: Animals; Aorta; Cimetidine; Dimaprit; Female; Histamine H2 Antagonists; Imidazoles; Impromidine; In Vitro Techniques; Male; Rabbits; Receptors, Histamine H2; Thiourea

In the present study the effects of three structurally different H2-receptor antagonists (cimetidine, ranitidine and oxmetidine) have been investigated on gastric acid and pepsin secretion of eight cats provided with cannulated gastric fistulas. The maximum pepsin output obtained from a set of complete dose-response curves of dimaprit was not statistically different from basal values. In the presence of the H2-antagonists, while the gastric acid secretion induced by dimaprit was competitively antagonized, the pepsin secretion was differently affected. The data obtained on pepsin activity with cimetidine and ranitidine were quite similar to the control values. By contrast, oxmetidine induced a significant increase. The results suggest a very weak involvement of the H2-receptors in pepsin activity and that oxmetidine performance could not be attributable to an H2-receptor block.

Topics: Animals; Cats; Cimetidine; Dimaprit; Dose-Response Relationship, Drug; Gastric Acid; Gastric Juice; Histamine H2 Antagonists; Imidazoles; Pepsin A; Ranitidine; Thiourea

Topics: Animals; Dimaprit; Guinea Pigs; Histamine H2 Antagonists; Ileum; Imidazoles; Impromidine; In Vitro Techniques; Methylhistamines; Muscle Contraction; Muscle, Smooth; Pyrimidinones; Receptors, Histamine; Receptors, Histamine H2; Thiourea