Rat hypothalamus contains an antimitogenic factor acting via benzodiazepine receptors.
The effect of crude rat hypothalamic extracts on the lymphocyte proliferation in vitro was investigated. It was found that hypothalamic extracts (HE) significantly inhibited the 3H-thymidine incorporation by the mouse spleen lymphocytes cultured in vitro. The factor (or factors) responsible for the antimitogenic effect is thermostabile and partially destroyable by trypsin digestion. The latter observation suggests that it is probably a peptide. Diazepam had been found to exert a similar antimitogenic effect on mouse spleen lymphocytes as HE. The putative endogenous benzodiazepine (BZD) receptor ligand is also assumed to be a peptide. The working hypothesis that the antimitogenic effect of HE depends on endogenous substance acting via BZD receptor was proposed. To test such a possibility, the interaction of HE and specific BZD receptor ligands Ro-15-1788 and Ro-5-4864 was investigated. It was found that Ro-5-4864 alone suppressed the lymphocyte proliferation, and the joint antiproliferative effect of HE and Ro-5-4864 was not additive. Ro-15-1788 alone did not influence the lymphocyte proliferation but abolished the antiproliferative effect of HE. These data suggest that antimitogenic factor present in HE acts via BZD receptors.
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D007031:Hypothalamus / Q000032:analysis*; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000037:antagonists & inhibitors*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D014020:Tissue Extracts / Q000494:pharmacology
D001570:Benzodiazepinones; D008024:Ligands; D008934:Mitogens; D010455:Peptides; D011963:Receptors, GABA-A; D014020:Tissue Extracts; C028513:4'-chlorodiazepam; D005442:Flumazenil