Suppression of natural killer cell activity by FG 7142, a benzodiazepine receptor "inverse agonist".
A dose-dependent (5-50 mg/kg) suppression of natural killer (NK) cell activity was observed 2 h after administration of the benzodiazepine receptor "inverse agonist" FG 7142 (N-methyl-beta-carboline-3-carboxamide), and was still manifest 24 h later. Addition of FG 7142 (1-1000 nM) to the 4 h 51 Cr release assay did not affect NK cell activity. Pretreatment of mice with the benzodiazepine receptor antagonist Ro 15-1788 (10 mg/kg) blocked FG 7142-induced suppression of NK cell activity, but had no effect when administered alone. The suppression of NK cell activity by FG 7142, a compound which produces a syndrome resembling stress or anxiety in both animals and man, provides further evidence that the central nervous system pathways subserved by the benzodiazepine/GABA receptor chloride channel complex ("supramolecular complex") may play a role in the modulation of immune function.
Petitto
J M
JM
Laboratory of Neuroscience, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Skolnick
P
P
Arora
P K
PK
D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D003601:Cytotoxicity Tests, Immunologic; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D007694:Killer Cells, Natural / Q000187:drug effects*; D008297:Male; D051379:Mice; D011963:Receptors, GABA-A / Q000187:drug effects / Q000276:immunology*
D002243:Carbolines; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D005442:Flumazenil; C035874:FG 7142