title: Differential effects of histamine receptor antagonists on human natural killer cell activity.
abstract: In this study we investigated the modulation of natural killer (NK) cell activity by various histamine receptor antagonists in vitro. The histamine H2-receptor antagonists cimetidine, ranitidine and tiotidine suppressed NK cell cytotoxicity (NKCC) at a high concentration (10(-3) M). Cimetidine enhanced NKCC of Ficoll-Hypaque-separated lymphocytes and of lymphocytes enriched for NKCC by Percoll density gradient centrifugation. The enhancing effect of cimetidine was dose-dependent at final concentrations of 10(-4)-10(-7) M and did not require the presence of adherent cells/monocytes. Ranitidine did not affect NKCC over a wide range of concentrations. Tiotidine strongly enhanced NKCC of low-density, large granular lymphocyte-enriched mononuclear cells (MNC) in the presence of adherent cells/monocytes, but was ineffective in nonadherent effector cells. All H2-receptor antagonists clearly antagonized histamine-induced NKCC enhancement in monocyte-containing effector cells. Clemastin, a specific H1-receptor antagonist, effectively suppressed NKCC. This effect was mimicked by a clemastin isomer with very low affinity for H1-receptors. We conclude that (1) cimetidine enhances NKCC in vitro by a mechanism of action that is not specifically related to antagonism of H2-receptors, (2) tiotidine displays mixed agonist/antagonist properties for MNC H2-receptors and (3) NK-suppressive properties of clemastin are unrelated to H1-receptor antagonism.
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002927:Cimetidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007372:Interferons / Q000096:biosynthesis / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D011899:Ranitidine / Q000494:pharmacology
chemical_list: D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D002927:Cimetidine; D011899:Ranitidine; D007372:Interferons; C023990:tiotidine