ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Phosphoinositide 3-kinase cascade facilitates mu-opioid desensitization in sensory neurons by altering G-protein-effector interactions.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The trial behind it
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- GRK2 Dictates a Functional Switch of the Peripheral Mu-Opioid Receptor.ACS chemical neuroscience · 2020Article
- Role of peripheral sensory neuron mu-opioid receptors in nociceptive, inflammatory, and neuropathic pain.Regional anesthesia and pain medicine · 2020Article
- The dark side of opioids in pain management: basic science explains clinical observation.Pain reports · 2016Article
- Stromal Cell-Derived Factor 1 Increases Tetrodotoxin-Resistant Sodium Currents Nav1.8 and Nav1.9 in Rat Dorsal Root Ganglion Neurons via Different Mechanisms.Neurochemical research · 2016Article
- Redox Regulation and the Autistic Spectrum: Role of Tryptophan Catabolites, Immuno-inflammation, Autoimmunity and the Amygdala.Current neuropharmacology · 2014Article
- Increased agonist affinity at the μ-opioid receptor induced by prolonged agonist exposure.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Regulation of μ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance.Pharmacological reviews · 2013Review
- μ-Opioid receptor desensitization: homologous or heterologous?The European journal of neuroscience · 2012Article
- Evidence that behavioral phenotypes of morphine in β-arr2-/- mice are due to the unmasking of JNK signaling.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2012Article
- Regulation of κ-opioid receptor signaling in peripheral sensory neurons in vitro and in vivo.The Journal of pharmacology and experimental therapeutics · 2011Article
- Analgesic tone conferred by constitutively active mu opioid receptors in mice lacking β-arrestin 2.Molecular pain · 2011Article
- Mu-opioid receptors transiently activate the Akt-nNOS pathway to produce sustained potentiation of PKC-mediated NMDAR-CaMKII signaling.PloS one · 2010Article
- Two distinct mechanisms mediate acute mu-opioid receptor desensitization in native neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- p38 MAPK and beta-arrestin 2 mediate functional interactions between endogenous micro-opioid and alpha2A-adrenergic receptors in neurons.The Journal of biological chemistry · 2009Article
- The activation of transient receptor potential vanilloid receptor subtype 1 by capsaicin without extracellular Ca2+ is involved in the mechanism of distinct substance P release in cultured rat dorsal root ganglion neurons.Naunyn-Schmiedeberg's archives of pharmacology · 2008Article
- Article
- Direct binding of p85 to sst2 somatostatin receptor reveals a novel mechanism for inhibiting PI3K pathway.The EMBO journal · 2006Article
- Impact of opiate-HIV-1 interactions on neurotoxic signaling.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2006Review
- Article
- Molecular targets of opiate drug abuse in neuroAIDS.Neurotoxicity research · 2005Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Signaling via G-protein-coupled receptors undergoes desensitization after prolonged agonist exposure. Here we investigated the role of phosphoinositide 3-kinase (PI3K) and its downstream pathways in desensitization of micro-opioid inhibition of neuronal Ca2+ channels. In cultured mouse dorsal root ganglion neurons, two mechanistically different forms of desensitization were observed after acute or chronic treatment with the micro agonist [D-Ala2, N-MePhe4, Gly-ol5]-enkephalin (DAMGO). Chronic DAMGO desensitization was heterologous in nature and significantly attenuated by blocking the activity of PI3K or mitogen-activated protein kinase (MAPK). A combined application of PI3K and MAPK inhibitors showed no additive effect, suggesting that these two kinases act in a common pathway to facilitate chronic desensitization. Acute DAMGO desensitization, however, was not affected by the inhibitors. Furthermore, upregulation of the PI3K-Akt pathway in mutant mice lacking phosphatase and tensin homolog, a lipid phosphatase counteracting PI3K, selectively enhanced chronic desensitization in a PI3K- and MAPK-dependent manner. Using the prepulse facilitation (PPF) test, we further examined changes in the voltage-dependent component of DAMGO action that requires direct interactions between betagamma subunits of G-proteins and Ca2+ channels. DAMGO-induced PPF was diminished after chronic treatment, suggesting disruption of G-protein-channel interactions. Such disruption could occur at the postreceptor level, because chronic DAMGO also reduced GTPgammaS-induced PPF that was independent of receptor activation. Again, inhibition of PI3K or MAPK reduced desensitization of PPF. Our data suggest that the PI3Kcascade involving MAPK and Akt enhances micro-opioid desensitization via postreceptor modifications that interfere with G-protein-effector interactions.
Indexed as
Identifiers
14614088PMC6741018W1513944968What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.