Age‐Dependent Changes in the Subcellular Distribution of Rat Brain μ‐Opioid Receptors and GTP Binding Regulatory Proteins

Wojciech, T.; Yeung, Sai‐Ching Jim; Belcheva, Mariana M.; Barg, Jacob; Coscia, Carmine J.

doi:10.1111/j.1471-4159.1991.tb06340.x

Cited by 18 publications

(15 citation statements)

References 36 publications

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“…The Na + ,K + -ATPase activity was enriched 5-fold in PM vs. total homogenates (4.99 ± 0.5 μmoles/mg protein/min in PM vs. 0.91 ± 0.2 μmoles/mg protein/minute in total homogenates). This enrichment of enzyme activity is consistent with earlier reports showing 4-to 5-fold higher activities of Na + ,K + -ATPase in brain PM vs. homogenates (51–53). We also examined for potential cytosolic contamination of the PM fraction by determining the activity of glutamine synthetase and found very low activity in the PM fraction (0.044 ± 0.002 μmoles/mg protein/hour) vs. total homogenates (0.63 ± 0.03 μmoles/mg protein/hour).…”

Section: Methodssupporting

confidence: 93%

Brain Aquaporin-4 in Experimental Acute Liver Failure

Rao

Jayakumar

Tong

et al. 2010

J Neuropathol Exp Neurol

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Intracranial hypertension due to brain edema and associated astrocyte swelling is a potentially lethal complication of acute liver failure (ALF). Mechanisms of edema formation are not well understood but elevated levels of blood and brain ammonia and its byproduct glutamine have been implicated in this process. We examined mRNA and protein expression of the water channel protein aquaporin-4 (AQP4) in cerebral cortex in a rat model of ALF induced by the hepatotoxin thioacetamide. Rats with ALF showed increased AQP4 protein in the plasma membrane (PM). Total tissue levels of AQP4 protein and mRNA levels were not altered indicating that increased AQP4 is not transcriptionally mediated but is likely due to a conformational change in the protein, i.e. a more stable anchoring of AQP4 to the PM and/or interference with its degradation. By immunohistochemistry there was an increase in AQP4 immunoreactivity in the PM of perivascular astrocytes in ALF. Rats with ALF showed increased levels of α-syntrophin, a protein involved in the anchoring of AQP4 to perivascular astrocytic end-feet. Increased AQP4 and α-syntrophin levels were inhibited by L-histidine, an inhibitor of glutamine transport into mitochondria, suggesting a role for glutamine in the increase of PM levels of AQP4. These results indicate that increased AQP4 PM levels in perivascular astrocytic end-feet are likely critical to the development of brain edema in ALF.

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Section: Methodssupporting

confidence: 93%

Brain Aquaporin-4 in Experimental Acute Liver Failure

Rao

Jayakumar

Tong

et al. 2010

J Neuropathol Exp Neurol

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“…This interpretation is supported by our findings on intracellular opioid sites isolated from neonatal brain and cells with up-regulated opioid receptors , which also display a greater Gpp(NH)p sensitivity. We have also discovered that neonatal microsomes contain more G protein than their adult counterpart (Bem et al, 1991). This is in accordance with the greater Gpp(NH)p sensitivity observed for P-3 than adult microsomes (Fig.…”

Section: Discussionsupporting

confidence: 87%

“…Brains of 3-day-old (P-3) pups were subjected to subcellular fractionation following the same procedure as for adults. Our previous marker enzymes studies on adult (Roth et al, 1981) and neonatal (Bem et al, 1991) membranes established that cross contamination between SPMs and microsomes was minimal and cannot account for the microsomal opioid binding.…”

Section: Subcellular Fractionation Of Rat Brainsmentioning

confidence: 98%

Differential coupling of opioid binding sites to guanosine triphosphate binding regulatory proteins in subcellular fractions of rat brain

Szücs

Coscia

1992

J of Neuroscience Research

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In this study, we present evidence for the occurrence of mu, delta, and kappa opioid binding sites in synaptic plasma membranes (SPM) and microsomes of rat brain. Binding to all three opioid classes was inhibited by 5'-guanylylimidodiphosphate (Gpp[NH]p) in SPM, while microsomal sites proved to be insensitive to this GTP analog. Sensitivity was restored upon solubilization of microsomes with digitonin, suggesting that opioid receptors are physically separated from G proteins in this fraction. Modulation of microsomal binding by Na+ and Mn++ was greater than that of SPM. Pertussis toxin-catalyzed adenosine diphosphate (ADP) ribosylation revealed the presence of G proteins with alpha-subunit molecular weights of 40 kDa in both subcellular fractions. Basal low Km GTPase activity in SPM was greater than in microsomes. Etorphine elicited a concentration-dependent stimulation of guanosine triphosphatase (GTPase) activity in SPMs but not in microsomes, indicating functional coupling of opioid receptors to G protein in the former and an uncoupling in the latter. Microsomes from 3-day-old rat brain contained more mu opioid sites and they were more sensitive to Gpp(NH)p inhibition than those in adults. These results are consistent with the hypothesis that opioid binding sites in adult microsomes are internalized and G protein uncoupled, while those in neonates are newly synthesized, coupled receptors.

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“…Indeed, it has long-been suggested that opioids modify CNS plasticity or disease through actions in astroglia (Ronnback and Hansson, 1988; Stiene-Martin et al, 1990; Stiene-Martin and Hauser, 1991; Deleo et al, 2004; Hauser et al, 2005; Narita et al, 2006; Hansson, 2006; Kim et al, 2006; Hauser et al, 2007; Hutchinson et al, 2011). However, it has been quite difficult to separate, especially in vivo, the actions of opioids on glia from their effects on neurons, since all neural cell types examined thus far can express functional opioid receptors including MOR (Stiene-Martin et al, 1991; Eriksson et al, 1991; Bem et al, 1991; Stiene-Martin and Hauser, 1991; Barg et al, 1992; Hauser et al, 1996; Stiene-Martin et al, 1998; Knapp et al, 1998; Miyatake et al, 2009). These cell types include neurons, astroglia, microglia, oligodendroglia, and glial progenitors (Hauser et al, 2009; Hahn et al, 2010), as well as support cells within the CNS such as endothelial cells and the connective tissue stroma surrounding large blood vessels, which can also express opioid receptors (see Hauser et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Morphine and gp120 Toxic Interactions in Striatal Neurons are Dependent on HIV-1 Strain

Podhaizer

Zou

Fitting

et al. 2011

J Neuroimmune Pharmacol

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A rigorously controlled, cell culture paradigm was used to assess the role of HIV-1 gp120 ± morphine in mediating opioid-HIV interactive toxicity in striatal neurons. Computerized time-lapse microscopy tracked the fate of individual neurons co-cultured with mixed-glia from mouse striata during opioid and gp120 exposure. Subpopulations of neurons and astroglia displayed μ-opioid receptor, CXCR4, and CCR5 immunoreactivity. While gp120 alone was or tended to be neurotoxic irrespective of whether X4-tropic gp120IIIB, R5-tropic gp120ADA, or dual-tropic gp120MN was administered, interactive toxicity with morphine differed depending on HIV-1 strain. For example, morphine only transiently exacerbated gp120IIIB-induced neuronal death; however, in combination with gp120MN, morphine caused sustained increases in the rate of neuronal death compared to gp120MN alone that were prevented by naloxone. Alternatively, gp120ADA significantly increased the rate of neuron death, which was unaffected by morphine. The transient neurotoxic interactions between morphine and gp120IIIB were abrogated in the absence of glia suggesting that glia contribute significantly to the interactive pathology with chronic opiate abuse and neuroAIDS. To assess how mixed-glia might contribute to the neurotoxicity, the effects of morphine and/or gp120 on the production of reactive oxygen species (ROS) and on glutamate buffering were examined. All gp120 variants, and to a lesser extent morphine, increased ROS and/or decreased glutamate buffering, but together failed to show any interaction with morphine. Our findings indicate that HIV-1 strain-specific differences in gp120 are critical determinants in shaping both the timing and pattern of neurotoxic interactions with opioid drugs.

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Age‐Dependent Changes in the Subcellular Distribution of Rat Brain μ‐Opioid Receptors and GTP Binding Regulatory Proteins

Cited by 18 publications

References 36 publications

Brain Aquaporin-4 in Experimental Acute Liver Failure

Brain Aquaporin-4 in Experimental Acute Liver Failure

Differential coupling of opioid binding sites to guanosine triphosphate binding regulatory proteins in subcellular fractions of rat brain

Morphine and gp120 Toxic Interactions in Striatal Neurons are Dependent on HIV-1 Strain

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