In vivo and in vitro modulation of central type benzodiazepine receptors by phosphatidylserine.
The in vivo and in vitro modulation of central benzodiazepine binding sites (BDZ-R) by phosphatidylserine purified from bovine cerebral cortex (BC-PS) was studied. Five days i.p. administration of 15 mg/kg/day of BC-PS liposomes increased the maximal number of binding sites (Bmax) for [3H]flunitrazepam in cerebral cortical membranes. In contrast, the density of hippocampal benzodiazepine recognition binding sites decreased. In cerebellar membranes, BC-PS treatment did not alter the characteristics of [3H]flunitrazepam binding. Similar experiments using phosphatidylcholine extracted from bovine brain (BC-PC) resulted in no changes in the [3H]flunitrazepam binding in the 3 neural structures studied. Confirming previous results, rats submitted to an acute swimming stress showed a decrease in the density of cerebral cortex BDZ-R. Animals treated with BC-PS liposomes before stress showed cortical [3H]flunitrazepam binding significantly below treated, unstressed animals but not below controls. The effects of BC-PS liposomes appeared to be selective for the central type of BDZ-R since no changes were observed in [3H]RO 5-4864 binding, a radioligand specific for the peripheral type BDZ-R. Preincubation of cerebral cortical and cerebellar synaptosomal membranes with BC-PS liposomes (1-300 micrograms per assay) significantly increased in a concentration-dependent manner (up to 100 micrograms) the [3H]flunitrazepam binding. Scatchard analysis revealed changes in the apparent affinity without alterations in the Bmax. Very similar results were obtained using a purified PS from spinal cord. BC-PC, phosphatidylinositol, phosphatidic acid and the lyso derivatives of PS and PC (lysoPS and lysoPC) were found to be ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)
Levi de Stein
M
M
Instituto de Biología Celular, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Medina
J H
JH
De Robertis
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E
D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003292:Convulsants / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007700:Kinetics; D008081:Liposomes; D010718:Phosphatidylserines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values
D001570:Benzodiazepinones; D003292:Convulsants; D008081:Liposomes; D010718:Phosphatidylserines; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D005445:Flunitrazepam