Chemistry/Biochemistry/Cell Biology/Pharmacology Core

化学/生物化学/细胞生物学/药理学核心

• 批准号: 7222484
• 负责人: Richard Irving Duclos
• 金额: $ 38.31万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-15 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7222484
• 关键词: 2-arachidonylglycerol; Address; Adenylate Cyclase; Affinity; Agonist; Amino Acids; Antibodies; Area; Behavioral; Behavioral Assay; Binding; Binding Sites; Biochemical; Biochemistry; Blood - brain barrier anatomy; Brain; CNR1 gene; CNR2 gene; Cannabinoids; Cellular biology; Characteristics; Chemicals; Chemistry; Class; Collaborations; Computer Simulation; Core Facility; Cultured Cells; Development; Drug Kinetics; Eating; Epitopes; Generations; Goals; Grant; High Pressure Liquid Chromatography; Human; I125 isotope; Image; Inhibitory Concentration 50; Intestinal Absorption; Label; Laboratories; Laboratory Research; Ligands; Mammalian Cell; Measures; Membrane; Metabolic; Microsomes; Monoacylglycerol Lipases; Motor Activity; Mus; Nature; Numbers; Octanols; Oocytes; Organ; Partition Coefficient; Penetration; Pharmacology; Phase; Plasma Proteins; Preparation; Principal Investigator; Production; Property; Protein Binding; Radiolabeled; Rattus; Research Personnel; Screening procedure; Signal Transduction; Site; Structure; Surface; Testing; Tritium; Water; analog; anandamide; arachidonoylethanolamide synthase; base; cannabinoid receptor; cost; cyclooxygenase 2; design; drug metabolism; fatty acid amide hydrolase; in vitro Assay; in vivo; inhibitor/antagonist; mutant; natural hypothermia; novel; programs; radioligand; radiotracer; receptor; receptor binding; research study; response

This Core Facility will serve as a technical and scientific support unit for the three projects (1, 2, 3) of this Program Project. Its major goals involve: (1) the production of radiolabeled and nonradiolabeled analogs in sufficient quantifies to address the needs of the research laboratories involved in the four projects; (2) the testing of all new analogs for their affinities for the CB1 and CB2 cannabinoid receptors, including the 125I- radiolabeled ligands; (3) the testing of the "successful covalent ligands" for their abilities to irreversibly bind to CB1 and CB2; (3) the biochemical and pharmacological characterization of the ligands; (5) the testing of ligands for their abilities to act as substrates or inhibitors of anandamide amidase (ANAase); (6) the development of epitope tagged CB1 and CB2 constructs and their expression in mammalian cells; and (7) the preparation of antibodies for the CB1 and CB2 receptors. Radiolabeled and non-radiolabeled compounds produced under the auspices of Core B will also be made available to other laboratories identified in this program project whose collaboration is at not cost to the grant. All successful ligands, reversible and irreversible, will be characterized biochemically andpharmacologically by determining their activities as agonists or antagonists. Biochemically, the analogs will be tested for: (a) their effects on GTPyS binding and adenylate cyclase and (b) their partitioning properties in the membrane. The pharmacological characterization will include in vivo bioassaysto measure the tetrad of behavioraltests characteristic of cannabinoid pharmacology including locomotor, hypothermia, antinociception and immobility. A representative group of compounds will also be examined for their ability to induce tolerance.

该核心基金将作为其中三个项目（1、2、3）的技术和科学支助单位