Effects of acute agonist treatment on subcellular distribution of κ opioid receptor in rat spinal cord

Wang, Yulin; Xu, Wei; Huang, Peng; Chavkin, Charles; Bockstaele, Elisabeth J. Van; Liu-Chen, Lee Yuan

doi:10.1002/jnr.21971

Cited by 17 publications

(16 citation statements)

References 37 publications

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“…Second, it is possible that a significant number of KOPR detected by [ 3 H]U69,593 binding in the present study may not be coupled functionally. Some of these KOPR binding sites may be localized intracellularly and not available for signal transduction (Wang et al, , 2009.…”

Section: Discussionmentioning

confidence: 99%

Sex Difference in κ-Opioid Receptor (KOPR)-Mediated Behaviors, Brain Region KOPR Level and KOPR-Mediated Guanosine 5′-O-(3-[35S]Thiotriphosphate) Binding in the Guinea Pig

Wang

Rasakham²,

Huang³

et al. 2011

The Journal of Pharmacology and Experimental Therapeutics

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We examined whether sex differences in -opioid receptor (KOPR) pharmacology exist in guinea pigs, which are more similar to humans in the expression level and distribution of KOPR in the brain than rats and mice. The KOPR agonist trans-(Ϯ)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)benzeneacetamide methanesulfonate (U50,488H) produced a dose-dependent increase in abnormal postures and immobility with more effects in males than females. Males also showed more U50,488H-induced antinociception in the paw pressure test than females. Pretreatment with the KOPR antagonist norbinaltorphimine blocked U50,488H-induced abnormal body postures and antinociception. In contrast, inhibition of cocaine-induced hyperambulation by U50,488H was more effective in females than males. Thus, sex differences in the effects of U50,488H are endpoint-dependent. We then examined whether sex differences in KOPR levels and KOPR-mediated G protein activation in brain regions may contribute to the observed differences using quantitative in vitro autora-

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Section: Discussionmentioning

confidence: 99%

Sex Difference in κ-Opioid Receptor (KOPR)-Mediated Behaviors, Brain Region KOPR Level and KOPR-Mediated Guanosine 5′-O-(3-[35S]Thiotriphosphate) Binding in the Guinea Pig

Wang

Rasakham²,

Huang³

et al. 2011

The Journal of Pharmacology and Experimental Therapeutics

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“…3D). Presynaptic effects of κ-OR activation have been described in other brain regions (Ackley et al, 2001; Bie and Pan, 2003; Drake et al, 1997; Hjelmstad and Fields, 2001; Ogura and Kita, 2000; Simmons and Chavkin, 1996; Svingos et al, 2001; Svingos and Colago, 2002; Svingos et al, 1999; Wang et al, 2009; Weisskopf et al, 1993). In many of these regions, glutamate, glycine, and GABA neurotransmission were targets of κ-OR-mediated presynaptic effects.…”

Section: Dynorphin and κ-Ors: Presynaptic Modulator Of Lc Activitymentioning

confidence: 93%

The locus coeruleus: A key nucleus where stress and opioids intersect to mediate vulnerability to opiate abuse

2010

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The interaction between the stress axis and endogenous opioid systems has gained substantial clinical attention as it is increasingly recognized that stress predisposes to opiate abuse. For example, stress has been implicated as a risk factor in vulnerability to the initiation and maintenance of opiate abuse and is thought to play an important role in relapse in subjects with a history of abuse. Numerous reports indicating that stress alters individual sensitivity to opiates suggest that prior stress can influence the pharmacodynamics of opiates that are used in clinical settings. Conversely, the effects of opiates on different components of the stress axis can impact on individual responsivity to stressors and potentially predispose individuals to stress-related psychiatric disorders. One site at which opiates and stress substrates may interact to have global effects on behavior is within the locus coeruleus (LC), the major brain norepinephrine (NE)-containing nucleus. This review summarizes our current knowledge regarding the anatomical and neurochemical afferent regulation of the LC. It then presents physiological studies demonstrating opposing interactions between opioids and stress-related neuropeptides in the LC and summarizes results showing that chronic morphine exposure sensitizes the LC-NE system to corticotropin releasing factor and stress. Finally, new evidence for novel presynaptic actions of kappa-opioids on LC afferents is provided that adds another dimension to our model of how this central NE system is co-regulated by opioids and stress-related peptides.

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“…The perimeter and area of each dendritic profle was obtained using Image J software (NIH). In addition, as with previous studies from our group (Reyes et al, 2006; Reyes et al, 2008; Wang et al, 2009), care was taken to ensure that control and experimental groups contained similarly sized profiles. We did not observe any statistical difference in the size of profiles analyzed in any group examined as we have recently reported (Reyes et al, 2010).…”

Section: Methodsmentioning

confidence: 99%

Opiate agonist-induced re-distribution of Wntless, a mu-opioid receptor interacting protein, in rat striatal neurons

Reyes

Vakharia

Ferraro

et al. 2012

Experimental Neurology

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Wntless (WLS), a mu-opioid receptor (MOR) interacting protein, mediates Wnt protein secretion that is critical for neuronal development. We investigated whether MOR agonists induce re-distribution of WLS within rat striatal neurons. Adult male rats received either saline, morphine or [D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO) directly into the lateral ventricles. Following thirty minutes, brains were extracted and tissue sections were processed for immunogold silver detection of WLS. In saline-treated rats, WLS was distributed along the plasma membrane and within the cytoplasmic compartment of striatal dendrites as previously described. The ratio of cytoplasmic to total dendritic WLS labeling was 0.70±0.03 in saline-treated striatal tissue. Morphine treatment decreased this ratio to 0.48±0.03 indicating a shift of WLS from the intracellular compartment to the plasma membrane. However, following DAMGO treatment, the ratio was 0.85±0.05 indicating a greater distribution of WLS intracellularly. The difference in the re-distribution of the WLS following different agonist exposure may be related to DAMGO’s well known ability to induce internalization of MOR in contrast to morphine, which is less effective in producing receptor internalization. Furthermore, these data are consistent with our hypothesis that MOR agonists promote dimerization of WLS and MOR, thereby preventing WLS from mediating Wnt secretion. In summary, our findings indicate differential agonist-induced trafficking of WLS in striatal neurons following distinct agonist exposure. Adaptations in WLS trafficking may represent a novel pharmacological target in the treatment of opiate addiction and/or pain.

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Effects of acute agonist treatment on subcellular distribution of κ opioid receptor in rat spinal cord

Cited by 17 publications

References 37 publications

Sex Difference in κ-Opioid Receptor (KOPR)-Mediated Behaviors, Brain Region KOPR Level and KOPR-Mediated Guanosine 5′-O-(3-[35S]Thiotriphosphate) Binding in the Guinea Pig

Sex Difference in κ-Opioid Receptor (KOPR)-Mediated Behaviors, Brain Region KOPR Level and KOPR-Mediated Guanosine 5′-O-(3-[35S]Thiotriphosphate) Binding in the Guinea Pig

The locus coeruleus: A key nucleus where stress and opioids intersect to mediate vulnerability to opiate abuse

Opiate agonist-induced re-distribution of Wntless, a mu-opioid receptor interacting protein, in rat striatal neurons

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