Effect of hypoosmotic stress on peripheral-type benzodiazepine receptors in cultured astrocytes.
Astrocytes appear to be the primary source of peripheral benzodiazepine (PBZD) receptors in brain. The function of this receptor is not well understood. Since there is evidence that this receptor may be involved in cell volume control, we examined the effect of hypoosmotic stress on the regulation of the PBZD receptors in homogenates of cultured astrocytes derived from neonatal rat cerebral cortex. Exposure of astrocytes that were maintained in the presence of dibutyryl cAMP (dBcAMP) to hypoosmotic medium (200 mOsm) for 24 h resulted in 27 and 57% increased in the number of [3H]PK 11195 and [3H]Ro5-4864-binding sites, respectively, as compared with isoosmotic media (320 mOsm). This receptor upregulation is osmolarity- and time-dependent. However, hypoosmotic stress had no effect on PBZD receptor-binding in astrocytes that were maintained in the absence of dBcAMP. Under isoosmotic conditions, dBcAMP appears to regulate [3H]Ro5-4864 but not [3H]PK 11195-binding sites, a finding which further supports a partial distinction between the binding sites labeled with these ligands. The modulation of PBZD receptors by hypoosmotic stress suggests a possible role for these receptor sites in astrocyte volume control.
Itzhak
Y
Y
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, FL 33101.
Bender
A S
AS
Norenberg
M D
MD
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001570:Benzodiazepinones / Q000493:pharmacokinetics; D003994:Bucladesine / Q000493:pharmacokinetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D003292:Convulsants / Q000493:pharmacokinetics; D007546:Isoquinolines / Q000493:pharmacokinetics; D009994:Osmolar Concentration; D011869:Radioligand Assay; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D014883:Water-Electrolyte Imbalance / Q000378:metabolism*
D001570:Benzodiazepinones; D003292:Convulsants; D007546:Isoquinolines; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D003994:Bucladesine; C037850:PK 11195