title: CRIP1a switches cannabinoid receptor agonist/antagonist-mediated protection from glutamate excitotoxicity.
abstract: A shared pathology among many neurological and neurodegenerative disorders is neuronal loss. Cannabinoids have been shown to be neuroprotective in multiple systems. However, both agonists and antagonists of the CB(1) cannabinoid receptor are neuroprotective, but the mechanisms responsible for these actions remain unclear. Recently a CB(1) receptor interacting protein, CRIP1a, was identified and found to alter CB(1) activity. Here we show that in an assay of glutamate neurotoxicity in primary neuronal cortical cultures CRIP1a disrupts agonist-induced neuroprotection and confers antagonist-induced neuroprotection.
authors: Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Health Sciences University, Augusta, GA 30912, USA.
authors: Brandon
authors: B
authors: Stauffer
authors: Kathleen T
authors: KT
authors: Wallis
authors: Steven P
authors: SP
authors: Wilson
authors: Michaela
authors: M
authors: Egertová
authors: Maurice R
authors: MR
authors: Elphick
authors: Deborah L
authors: DL
authors: Lewis
authors: Lori Redmond
authors: LR
authors: Hardy
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology; D015153:Blotting, Western; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002352:Carrier Proteins / Q000494:pharmacology*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D018846:Excitatory Amino Acids / Q000633:toxicity*; D005822:Genetic Vectors; D018698:Glutamic Acid / Q000633:toxicity*; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D018696:Neuroprotective Agents; D010880:Piperidines / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D060888:Real-Time Polymerase Chain Reaction; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis; D000077285:Rimonabant; D016704:Synapsins / Q000378:metabolism
chemical_list: D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002352:Carrier Proteins; C540799:Cnrip1 protein, rat; D018846:Excitatory Amino Acids; D009025:Morpholines; D009281:Naphthalenes; D018696:Neuroprotective Agents; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D016704:Synapsins; D018698:Glutamic Acid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077285:Rimonabant