Effect of benzodiazepines on the proliferation of mouse spleen lymphocytes in vitro.
The effect of several benzodiazepines (clonazepam, diazepam, Ro 5-4864, Ro 15-1788) and two pineal gland indoleamines (N-acetylserotonin, melatonin) on the spontaneous proliferation of mouse spleen lymphocytes was estimated in vitro by the 3 H-thymidine uptake assay. It was found that diazepam and Ro 5-4864 (a selective peripheral-type benzodiazepine receptor ligand) produced the concentration-dependent inhibition of 3 H-thymidine incorporation into the DNA of these cells. Ro 15-1788, a specific central-type receptor ligand, evoked a slight inhibitory effect in a high concentration (10(-4) M), whereas clonazepam did not produce any significant inhibition. When Ro 5-4864 was tested in combination with diazepam, the inhibition of lymphocyte proliferation did not exceed the effect of diazepam given alone. Ro 15-1788 was unable to reverse the inhibitory action of diazepam in the same experimental conditions. Melatonin and its precursor N-acetylserotonin tested in the concentration range of 10(-4)-10(-8) M had no significant influence on the spleen lymphocyte DNA replication in our assay system. These data suggest that diazepam inhibition of lymphocyte proliferation is mediated by peripheral-type sites. Additionally, the fact that melatonin and N-acetylserotonin were unable to affect 3 h-thymidine incorporation argues against any benzodiazepine receptor mediated effect of pineal indoleamines on a cellular proliferation.
Pawlikowski
M
M
Department of Experimental Endocrinology, Medical Academy of Lódź, Poland.
Lysoń
K
K
Kunert-Radek
J
J
Stepień
H
H
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D012016:Reference Values; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D012701:Serotonin; D008550:Melatonin; C006389:N-acetylserotonin