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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Benzodiazepine receptors and cerebrospinal fluid formation.

There is autoradiographic evidence that peripheral-type benzodiazepine ligands bind with high affinity to the membranes of choroid plexus tissue. In this study, the binding of a 4'-chloro analog of diazepam (Ro 5-4864) to rabbit choroid plexus and cerebral cortex was accomplished utilizing an in vitro radioactive assay method. A kinetic analysis of this binding revealed a relatively high affinity of this ligand (KD) for peripheral binding sites in plexus tissue (KD = 16.1 nM/mg protein). There was a 4.6-fold greater density of binding sites (total receptor density (Bmax) = 2.3 pmol/mg) in choroidal membrane as compared to cortical tissue (Bmax = 0.5 pmol/mg). In 40 rabbits in which a ventricular perfusion system was used, the rate of cerebrospinal fluid (CSF) formation was observed to decrease some 48% in the presence of 10(-4) M Ro 5-4864, although some inhibition of secretory activity was still noted at a CSF concentration of 10(-8) M. The choroid plexus tissue levels of adenosine 3',5'cyclic monophosphate (cAMP) and adenosine triphosphatase (ATPase) were not affected by 10(-4) M Ro 5-4864. The results of this study support the notion that the specific benzodiazepine peripheral binding sites in choroid plexus serve to modulate CSF formation. The mechanism of action is poorly understood but does not involve the transport ATPase system or the second messenger cAMP.[1]


  1. Benzodiazepine receptors and cerebrospinal fluid formation. Williams, G.L., Pollay, M., Seale, T., Hisey, B., Roberts, P.A. J. Neurosurg. (1990) [Pubmed]
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