RGD Reference Report - Opioid receptor agonists enhance the phosphorylation state of Fas-associated death domain (FADD) protein in the rat brain: functional interactions with casein kinase Ialpha, Galpha(i) proteins, and ERK1/2 signaling. - Rat Genome Database

RGD Reference Report - Opioid receptor agonists enhance the phosphorylation state of Fas-associated death domain (FADD) protein in the rat brain: functional interactions with casein kinase Ialpha, Galpha(i) proteins, and ERK1/2 signaling. - Rat Genome Database

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Opioid receptor agonists enhance the phosphorylation state of Fas-associated death domain (FADD) protein in the rat brain: functional interactions with casein kinase Ialpha, Galpha(i) proteins, and ERK1/2 signaling.
Authors:	Garcia-Fuster, MJ Ramos-Miguel, A Miralles, A Garcia-Sevilla, JA
Citation:	Garcia-Fuster MJ, etal., Neuropharmacology. 2008 Oct;55(5):886-99. doi: 10.1016/j.neuropharm.2008.06.071. Epub 2008 Jul 9.
RGD ID:	10059657
Pubmed:	PMID:18657552 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.neuropharm.2008.06.071 (Journal Full-text)
Opioid drugs have been proposed to promote anti-apoptotic signals in brain through inhibition of FADD protein [Garcia-Fuster et al., 2007. Effects of opiate drugs on Fas-associated protein with death domain (FADD) and effector caspases in the rat brain: Regulation by the ERK1/2 MAP kinase pathway. Neuropsychopharmacology 32, 399-411]. FADD phosphorylation by casein kinase Ialpha (CKIalpha) appears to regulate its non-apoptotic activity. This study investigated the effects of opioids on p-FADD in rat brain, as well as various mechanisms that could link opioid receptors with p-FADD, including the modulation of CKIalpha, Galpha(i) proteins and ERK1/2 signaling. In rat, mouse and human brains, various anti-p-FADD antibodies immunodetected the monomeric and oligomeric forms of this protein, irrespective of the antibody origin and specific Ser191 or Ser194 phosphorylation site. Acute mu- and delta-agonists increased, through specific opioid receptor mechanisms, the content of oligomeric and monomeric p-FADD forms in rat cortical homogenates (25-61%) and subcellular compartments, with most relevant effects for sufentanil in membrane (239%) and nucleus (136%). p-FADD induction vanished with repeated (5days) morphine but not SNC-80, and opioid withdrawal induced a new (morphine) or sustained (SNC-80) stimulatory effect (32-33%). The kappa-agonist (-)-U-50488H failed to stimulate p-FADD. Sufentanil reduced CKI protein and kinase activity in the cytosol (30-37%). Morphine, but not SNC-80, augmented CKIalpha in cytosol, membrane and nucleus (36-104%). In contrast to FADD, the ability of SNC-80 to stimulate p-FADD was not sensitive to ERK1/2 blockade. Pertussis toxin did not prevent the opposite effects of SNC-80 on p-FADD and FADD because the toxin by itself markedly altered their basal contents, indicating that FADD could be a novel toxin target. The upregulation of p-FADD induced by mu/delta-agonists could play a relevant role in the anti-apoptotic and/or neuroplastic effects of opioids.

Objects referenced in this article

Gene	Csnk1a1	casein kinase 1, alpha 1	Rattus norvegicus

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