Linked Life Data

6132001

Source:http://linkedlifedata.com/resource/pubmed/id/6132001

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1983-5-27
pubmed:abstractText
The binding of the novel ligand [3H]Ro 5-4864 to membrane preparations of rat kidney and brain was studied. [3H]Ro 5-4864 binds with high affinity (Kd = 0.6 nM) to a single saturable population of benzodiazepine recognition sites on renal membranes. Binding is rapidly reversible and, based on its pharmacological spectrum, takes place at the peripheral-type, Ro 5-4864-sensitive receptor. Specific high-affinity (Kd = 1.1 nM) [3H] Ro 5-4864 binding to the peripheral-type benzodiazepine binding site can also be demonstrated using rat brain membranes. [3H] Ro 5-4864 lacks stereospecificity with regard to chiral activity in position 3. A comparison of benzodiazepine inhibitory potency and structural features reveals that whereas a 4'-substitution assures specificity for the peripheral-type receptor, an N-methyl moiety is essential for optimal activity. [3H]Ro 5-4864 binding to brain membranes is temperature sensitive and is not modulated by barbiturates, convulsants, gamma-aminobutyric acid and chloride anions. The pyrazolopyridine derivative tracazolate inhibits [3H] Ro 5-4864 binding. The regional and subcellular distribution of binding is distinctly different from that previously demonstrated for [3H]benzodiazepine binding in the brain. The olfactory bulb shows the highest binding density, whereas the cerebral cortical, striatal and hippocampal areas are lowest among those areas studied. In the brain, [3H]Ro 5-4864 binding was found to sediment with the nuclear fraction. In conclusion, the present study shows that [3H]Ro 5-4864 is a selective ligand of the peripheral-type benzodiazepine binding site that can unequivocally be demonstrated in the kidney as well as the brain. The physiological significance of these findings, however, remain to be established.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
225
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
61-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1983
pubmed:articleTitle
Specific high-affinity binding sites for [3H]Ro 5-4864 in rat brain and kidney.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't