Suppression of cytotoxic T lymphocyte (CTL) activity by FG 7142, a benzodiazepine receptor 'inverse agonist'.
A dose-dependent (12.5-100 mg/kg) suppression of cytotoxic T lymphocyte (CTL) activity was observed in mice after administration of the benzodiazepine receptor 'inverse agonist' FG 7142 (N-methyl-beta-carboline-3-carboxamide). This compound produces a syndrome resembling stress or anxiety in both animals and man. Addition of FG 7142 (1-1000 nM) to either a 4-hour 51Chromium-release assay or 5-day in vitro CTL generation system did not affect CTL activity. Pretreatment with the benzodiazepine receptor antagonist Ro 15-1788 (10 mg/kg) attenuated FG 7142-induced suppression of CTL activity, but had no effect when administered alone. Time-course studies indicated that FG 7142-induced suppression of CTL activity was long-lasting. The suppression of CTL activity by FG 7142 provides further evidence that the central nervous system pathways subserved by the benzodiazepine/GABA receptor chloride channel complex may play an important role in the modulation of immune function.
Arora
P K
PK
Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892.
Hanna
E E
EE
Skolnick
P
P
D000818:Animals; D002243:Carbolines / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D007166:Immunosuppressive Agents; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
D002243:Carbolines; D007166:Immunosuppressive Agents; D011963:Receptors, GABA-A; D005442:Flumazenil; C035874:FG 7142