Biomaterial Database

Characterization of benzodiazepine receptors in the cerebellum. 2000

J Lameh, and P Wang, and D Meredith, and S L Shafer, and G H Loew

Molecular Research Institute, Mountain View, CA 94034-2316, USA.

1. The goals of the work reported here were to further characterize benzodiazepine/GABA(A) (BDZR) receptor heterogeneity in the cerebellum and to measure the affinities and selectivities of structurally diverse benzodiazepines at each site identified. 2. Five chemical families were included in these studies. These were 1,4-benzodiazepines (flunitrazepam), imidazobenzodiazepines (RO15-1788 and RO15-4513 and RO16-6028), beta-carbolines (Abecarnil) and pyrazoloquinolines (CGS 8216, CGS 9895 and CGS 9896). 3. Saturation and competition binding assays were combined with powerful data analysis software developed in our laboratory. Among the capabilities of this software is the identification of multiple binding sites for a cold ligand using a non-selective labeled ligand that binds with equal, but high, affinity to all the binding sites 4. Saturation binding assays using either [3H]-RO15-1788 or [3H]-RO15-4513 revealed only one apparent binding site, with a higher affinity for RO15-4513 than for RO15-1788. However, using [3H]-RO15-4513 for the competition binding studies in the cerebellum, together with our data analysis software, led to the identification of two distinct binding sites with equal densities for the diverse benzodiazepines studied. 5. In rat cerebellum one of the sites identified corresponds to GABA(A) receptors exhibiting alpha1 subunit pharmacology and the other to GABA(A) receptors exhibiting alpha6 subunit pharmacology. In general, the diverse families of BDZR ligands studied had much lower affinities for the alpha6 containing receptors.

UI	MeSH Term	Description	Entries
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D011963	Receptors, GABA-A	Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.	Benzodiazepine-Gaba Receptors,GABA-A Receptors,Receptors, Benzodiazepine,Receptors, Benzodiazepine-GABA,Receptors, Diazepam,Receptors, GABA-Benzodiazepine,Receptors, Muscimol,Benzodiazepine Receptor,Benzodiazepine Receptors,Benzodiazepine-GABA Receptor,Diazepam Receptor,Diazepam Receptors,GABA(A) Receptor,GABA-A Receptor,GABA-A Receptor alpha Subunit,GABA-A Receptor beta Subunit,GABA-A Receptor delta Subunit,GABA-A Receptor epsilon Subunit,GABA-A Receptor gamma Subunit,GABA-A Receptor rho Subunit,GABA-Benzodiazepine Receptor,GABA-Benzodiazepine Receptors,Muscimol Receptor,Muscimol Receptors,delta Subunit, GABA-A Receptor,epsilon Subunit, GABA-A Receptor,gamma-Aminobutyric Acid Subtype A Receptors,Benzodiazepine GABA Receptor,Benzodiazepine Gaba Receptors,GABA A Receptor,GABA A Receptor alpha Subunit,GABA A Receptor beta Subunit,GABA A Receptor delta Subunit,GABA A Receptor epsilon Subunit,GABA A Receptor gamma Subunit,GABA A Receptor rho Subunit,GABA A Receptors,GABA Benzodiazepine Receptor,GABA Benzodiazepine Receptors,Receptor, Benzodiazepine,Receptor, Benzodiazepine-GABA,Receptor, Diazepam,Receptor, GABA-A,Receptor, GABA-Benzodiazepine,Receptor, Muscimol,Receptors, Benzodiazepine GABA,Receptors, GABA A,Receptors, GABA Benzodiazepine,delta Subunit, GABA A Receptor,epsilon Subunit, GABA A Receptor,gamma Aminobutyric Acid Subtype A Receptors
D002531	Cerebellum	The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.	Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001667	Binding, Competitive	The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.	Competitive Binding
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus