title: Significant inhibition of spontaneous IgA secretion by selective peripheral-type benzodiazepine receptor ligands.
abstract: The in vitro effect of benzodiazepine (BZ) receptor ligands on the secretion of immunoglobulin isotypes IgM, IgG, and IgA by human peripheral blood mononuclear cells (PBMCs) was examined. It was found that the specific peripheral-type BZ receptor (PBR) ligands (Ro5-4864 and PK 11195) inhibit the spontaneous secretion of IgA by human PBMCs in a dose-dependent manner, in the micromolar range. The decreased secretion of IgG and IgM induced by these ligands did not reach significant levels. The mixed BZ ligands (diazepam and flunitrazepam) had no consistent or significant effect on the production of the three immunoglobulin isotypes tested in the current study. The central-type ligand (clonazepam) did not affect IgM, IgG, or IgA secretion. The significant inhibitory effect of PBR ligands was confined to the spontaneous secretion of IgA by human PBMCs, and no such effect was detected in cells stimulated by pokeweed mitogen to produce immunoglobulins. It seems that PBR ligands are capable of suppressing spontaneous IgA secretion, but fail to affect the augmented production induced by mitogen.
authors.affiliation: Hematology and Immunology Research Laboratory, Rabin Medical Center, Petah Tiqva, Israel.
authors.forename: H
authors.initials: H
authors.lastname: Bessler
authors.forename: B
authors.initials: B
authors.lastname: Caspi
authors.forename: M
authors.initials: M
authors.lastname: Gavish
authors.forename: M
authors.initials: M
authors.lastname: Rehavi
authors.forename: A
authors.initials: A
authors.lastname: Weizman
mesh_terms: D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000921:Antibody-Producing Cells / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002998:Clonazepam / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D005445:Flunitrazepam / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects
chemical_list: D014151:Anti-Anxiety Agents; D058787:GABA-A Receptor Antagonists; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007546:Isoquinolines; D002998:Clonazepam; D005445:Flunitrazepam; D003975:Diazepam; C037850:PK 11195