Propofol selectively alters GluA1 AMPA receptor phosphorylation in the hippocampus but not prefrontal cortex in young and aged mice.

Propofol is a commonly used general anesthetic agent which has been previously shown to enhance the inhibitory GABAergic transmission in the central nervous system. In addition to the GABAergic element, the excitatory transmission may be another central molecular site impacted by propofol. Increasing evidence implies that the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor represents an excitatory amino acid receptor subtype subjected to the regulation by propofol.

Endocrine effects of chronic opioid therapy: implications for clinical management.

SUMMARY Over the past few decades, the use of opioids in the management of chronic pain conditions has greatly increased. As opioid utilization has expanded, so has the recognition of associated hormonal derangements. These hormonal disturbances involve disruption, predominantly of the hypothalamic-pituitary-gonadal axis, and can affect both men and women treated with opioids.

Roles of subunit phosphorylation in regulating glutamate receptor function.

Protein phosphorylation is an important mechanism for regulating ionotropic glutamate receptors (iGluRs). Early studies have established that major iGluR subtypes, including α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors and N-methyl-d-aspartate (NMDA) receptors, are subject to phosphorylation. Multiple serine, threonine, and tyrosine residues predominantly within the C-terminal regions of AMPA receptor and NMDA receptor subunits have been identified as sensitive phosphorylation sites.

Rapid and sustained GluA1 S845 phosphorylation in synaptic and extrasynaptic locations in the rat forebrain following amphetamine administration.

The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is a major ionotropic glutamate receptor subtype in the mammalian brain. Like other glutamate receptors, the AMPA receptor is regulated by phosphorylation. By phosphorylating specific serine resides in AMPA receptor subunits (GluA1 and GluA2), various protein kinases regulate subcellular/subsynaptic expression and function of the receptor.

Regulation of phosphorylation of synaptic and extrasynaptic GluA1 AMPA receptors in the rat forebrain by amphetamine.

The AMPA receptor is regulated by phosphorylation. Two major phosphorylation sites (S831 and S845) are located in the intracellular C-terminal tail of GluA1 subunits. The phosphorylation on these sites controls receptor expression and function and is subject to the regulation by psychostimulants.

Phosphorylation and feedback regulation of metabotropic glutamate receptor 1 by calcium/calmodulin-dependent protein kinase II.

The metabotropic glutamate receptor 1 (mGluR1) is a Gα(q)-protein-coupled receptor and is distributed in broad regions of the mammalian brain. As a key element in excitatory synaptic transmission, the receptor regulates a wide range of cellular and synaptic activities. In addition to regulating its targets, the receptor itself is believed to be actively regulated by intracellular signals, although underlying mechanisms are essentially unknown.

Amphetamine increases phosphorylation of MAPK/ERK at synaptic sites in the rat striatum and medial prefrontal cortex.

Mitogen-activated protein kinases (MAPKs) play a central role in cell signaling. Extracellular signal-regulated kinase (ERK) is a prototypic subclass of MAPKs and is densely expressed in postmitotic neurons of adult mammalian brains. Active ERK translocates into the nucleus to regulate gene expression.

Upregulation of Npas4 protein expression by chronic administration of amphetamine in rat nucleus accumbens in vivo.

The neuronal PAS domain protein 4 (Npas4) is a transcription factor that is almost exclusively expressed in the mammalian brain. As an activity-dependent transcription factor, Npas4 regulates the transcription of discrete genes and transcriptionally controls the experience-dependent learning and memory. In this study, we explored the impact of the psychostimulant amphetamine (AMPH) on Npas4 protein expression in the rat striatum.

Non-analgesic effects of opioids: opioids and the endocrine system.

Opioids are among the oldest known and most widely used analgesics. The application of opioids has expanded over the last few decades, especially in the treatment of chronic non-malignant pain. This upsurge in opioid use has been accompanied by the increasingly recognized occurrence of opioid-associated endocrinopathy.

Modulation of ionotropic glutamate receptors and Acid-sensing ion channels by nitric oxide.

Ionotropic glutamate receptors (iGluR) are ligand-gated ion channels and are densely expressed in broad areas of mammalian brains. Like iGluRs, acid-sensing ion channels (ASIC) are ligand (H(+))-gated channels and are enriched in brain cells and peripheral sensory neurons. Both ion channels are enriched at excitatory synaptic sites, functionally coupled to each other, and subject to the modulation by a variety of signaling molecules.

WITHDRAWN: Upregulation of conventional protein kinase C phosphorylation and translocation in the rat nucleus accumbens following cocaine administration.

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Protection against protein aggregation by alpha-crystallin as a mechanism of preconditioning.

Anesthetic preconditioning occurs when cells previously exposed to inhaled anesthetics are protected against subsequent injury. We hypothesize that inhaled anesthetics may cause slight protein misfolding that involves site-specific dehydration, stimulating cytoprotective mechanisms. Human neuroblastoma cells were exposed to ethanol (as the dehydration agent) followed by quantitative analysis of the expression of five heat shock genes: DNAJC5G, CRYAA, HSPB2, HSF4 and HSF2.

Dynamic loss of surface-expressed AMPA receptors in mouse cortical and striatal neurons during anesthesia.

Ionotropic glutamate receptors, especially the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subtype, undergo dynamic trafficking between the surface membrane and intracellular organelles. This trafficking activity determines the efficacy and strength of excitatory synapses and is subject to modulation by changing synaptic inputs. Given the possibility that glutamate receptors in the central nervous system might be a sensitive target of anesthetic agents, this study investigated the possible impact of anesthesia on trafficking and subcellular expression of AMPA receptors in adult mouse brain neurons in vivo.

Isoflurane's Effect on Protein Conformation as a Proposed Mechanism for Preconditioning.

Persistent alteration of protein conformation due to interaction with isoflurane may be a novel molecular aspect of preconditioning. We preincubated human serum albumin with isoflurane, dialyzed to release agent, and assessed protein conformation. Susceptibility to chemical modification by methylglyoxal and nitrophenylacetate was also examined.

Isoflurane preconditioning involves upregulation of molecular chaperone genes.

Isoflurane preconditioning is a phenomenon in which cells previously exposed to isoflurane exhibit protection against subsequent noxious stimuli. We hypothesize that isoflurane may cause subtle protein misfolding that persists at a sublethal level, stimulating cytoprotective mechanisms. Human neuroblastoma cells (SH-SY5Y) were exposed to isoflurane followed by quantitative analysis of the expression of several families of heat shock genes (84 total transcripts).

Cocaine increases phosphorylation of MeCP2 in the rat striatum in vivo: a differential role of NMDA receptors.

Methyl CpG-binding protein-2 (MeCP2) is a transcriptional regulator that binds to methylated DNA at CpG sites and functions to silence DNA transcription. MeCP2 is subject to the phosphorylation modification at serine 421 (S421), which releases MeCP2 from DNA and thus facilitates gene expression. As a transcriptional repressor densely expressed in limbic reward circuits of adult mammalian brains, MeCP2 is recently emerging as a critical epigenetic factor in experience-dependent neural plasticity and psychostimulant addiction.

The endocrine effects of long-term oral opioid therapy: a case report and review of the literature.

The negative effects of long-term opioid administration on the body's endocrine system have been known for decades. These effects have been observed and studied with the use of intrathecal opioids and in heroin addicts. However, they have also been noted to occur with the use of oral opioids, especially in those patients who require chronic opioids for the management of nonmalignant and cancer-associated pain.

Post-translational modification biology of glutamate receptors and drug addiction.

Post-translational covalent modifications of glutamate receptors remain a hot topic. Early studies have established that this family of receptors, including almost all ionotropic and metabotropic glutamate receptor subtypes, undergoes active phosphorylation at serine, threonine, or tyrosine residues in their intracellular domains. Recent evidence identifies several glutamate receptor subtypes to be direct substrates for palmitoylation at cysteine residues.

Reversible palmitoylation regulates surface stability of AMPA receptors in the nucleus accumbens in response to cocaine in vivo.

Background: Palmitoylation is emerging as one of the most important posttranslational modifications of excitatory synaptic proteins in mammalian brain cells. As a reversible and regulatable modification sensitive to changing synaptic inputs, palmitoylation of ionotropic glutamate receptors contributes not only to the modulation of normal receptor and synaptic activities but also to the pathogenesis of various neuropsychiatric disorders. Here we report that palmitoylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is regulated by the psychostimulant, cocaine, and such regulation is involved in cocaine action.

Inhaled Anesthetics Promote Albumin Dimerization through Reciprocal Exchange of Subdomains.

Inhaled anesthetics affect protein-protein interaction, but the mechanisms underlying these effects are still poorly understood. We examined the impact of sevoflurane and isoflurane on the dimerization of human serum albumin (HSA), a protein with anesthetic binding sites that are well characterized. Intrinsic fluorescence emission was analyzed for spectral shifting and self-quenching, and control first derivatives (spectral responses to changes in HSA concentration) were compared against those obtained from samples treated with sevoflurane or isoflurane.

Carnosine protects against the neurotoxic effects of a serotonin-derived melanoid.

Anesthesia-related postoperative cognitive dysfunction (POCD) leads to morbidity in the elderly. Lipid peroxidative byproducts (i.e.

Decoding BDNF-LTP coupling in cocaine addiction.

BDNF is a neurotrophic peptide that regulates synaptic plasticity. New work by Lu and coworkers in this issue of Neuron now identifies BDNF as a gatekeeper of synaptic and behavioral plasticity in cocaine sensitization. In the medial prefrontal cortex, upregulated BDNF facilitates LTP and contributes to neurobehavioral adaptations to psychostimulants.

Alterations in subcellular expression of acid-sensing ion channels in the rat forebrain following chronic amphetamine administration.

Acid-sensing ion channels (ASICs) are densely expressed in broad areas of mammalian brains and actively modulate synaptic transmission and a variety of neuronal activities. To explore whether ASICs are linked to addictive properties of drugs of abuse, we investigated the effect of the psychostimulant amphetamine on subcellular ASIC expression in the rat forebrain in vivo. Repeated administration of amphetamine (once daily for 7 days, 1.

CaMKIIalpha interacts with M4 muscarinic receptors to control receptor and psychomotor function.

Muscarinic acetylcholine receptors (mAChRs) are widely expressed in the mammalian brain and are essential for neuronal functions. These receptors are believed to be actively regulated by intracellular signals, although the underlying mechanisms are largely unknown. In this study, we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) binds directly and selectively to one of five mAChR subtypes, M4 receptors (M4Rs), at their C-terminal regions of second intracellular loops.