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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.

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.