Prenatal diazepam induced persisting downregulation of peripheral (omega 3) benzodiazepine receptors on rat splenic macrophages.
Prenatal treatment with a low dose of diazepam (1.25 mg/kg/d, gestational day 14-20) has previously been found to cause longterm impairment of cellular immune responses in rat offspring. A possible site of action of diazepam, i.e., the peripheral-type (omega 3) benzodiazepine receptor, was characterized on splenic macrophages as well as on a rat splenic cell preparation containing mainly lymphocytes. In membranes of both preparations, [3H]PK 11195 bound to a single site which in competition experiments exhibited characteristics of the (omega 3) site. Prenatal exposure to diazepam was followed, at 8 weeks of life, by a marked decrease in maximal binding capacity (Bmax) of spleen macrophage membranes in offspring of both sexes, while membranes of the splenic cell preparation exhibited an increase of the dissociation constant of [3H]PK 11195 at 2 and 8 weeks of life. Both types of delayed effects may reduce the metabolic capacity of these immune cells, in which we have also observed deficits of cytokine release.
Institute of Pharmacology, University of Zürich, Switzerland.
M
M
Schlumpf
R
R
Parmar
W
W
Lichtensteiger
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D001665:Binding Sites; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology*; D015536:Down-Regulation; D005260:Female; D007546:Isoquinolines / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014316:Tritium
D007546:Isoquinolines; D011963:Receptors, GABA-A; D014316:Tritium; D003975:Diazepam; C037850:PK 11195