Influence of chronic morphine treatment on protein kinase C activity: comparison with butorphanol and implication for opioid tolerance

Narita, Minoru; Makimura, Mizue; Feng, Yun; Hoskins, Beth; Ho, Ing K.

doi:10.1016/0006-8993(94)90224-0

Cited by 85 publications

(29 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that protein kinase C (PKC) stimulates AC2, AC5, and AC7 in neuronal and non-neuronal cell lines and is implicated in morphine tolerance (Narita et al, 1994). We next sought to determine whether cAMP superactivation requires PKC.…”

Section: Resultsmentioning

confidence: 99%

Up-Regulation of AGS3 during Morphine Withdrawal Promotes cAMP Superactivation via Adenylyl Cyclase 5 and 7 in Rat Nucleus Accumbens/Striatal Neurons

et al. 2009

View full text Add to dashboard Cite

Effective medical treatment of opiate addiction is limited by a high relapse rate in abstinent addicts. Opiate withdrawal causes cAMP superactivation, but the underlying molecular mechanisms are not clear. Recent evidence implicates an activator of G-protein signaling 3 (AGS3) in opiate addiction. We found previously that during a 10-min activation of opioid receptors, AGS3 binds G␣ i -GDP to promote free G␤␥ stimulation of adenylyl cyclase (AC) 2 and 4, and/or inactivate G␣ i inhibitory function, thereby transiently enhancing cAMP-dependent protein kinase A (PKA) activity. In contrast, we report here that in nucleus accumbens/striatal neurons, morphine withdrawal induces cAMP superactivation, which requires up-regulation of AGS3. cAMP increases as a function of withdrawal time, by approximately 20% at 10 min and 75% at 5 h. However, cAMP superactivation does not require G␤␥. Instead, adenosine A2A receptor activation of G␣ s/olf seems to initiate cAMP superactivation and promote AGS3 up-regulation. Elevated AGS3 binds to G␣ i to prevent its inhibition on AC activation. Moreover, withdrawal-induced increases in cAMP/PKA activate phospholipase C and protein kinase C to further stimulate AC5 and AC7, causing cAMP superactivation. Our findings identify a critical role for AC 5 and 7 and A2A receptors for up-regulation of AGS3 in morphine withdrawal-induced cAMP superactivation.

show abstract

Section: Resultsmentioning

confidence: 99%

Up-Regulation of AGS3 during Morphine Withdrawal Promotes cAMP Superactivation via Adenylyl Cyclase 5 and 7 in Rat Nucleus Accumbens/Striatal Neurons

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Several protein kinases such as PKC [40], PKA [42], and ERK [43] have been suggested to be involved in OPRM1 desensitization. After morphine treatment, increases in PKC or ERK activities have been reported [44,45]. Although only chronic but not acute treatment of morphine could up-regulate PKA activity [46], all three protein kinases have been shown to phosphorylate OPRM1, thus resulting in receptor desensitization [17,[47][48][49].…”

Section: Discussionmentioning

confidence: 99%

Morphine-induced μ-opioid receptor rapid desensitization is independent of receptor phosphorylation and β-arrestins

Chu

Zheng

Loh

et al. 2008

Cellular Signalling

View full text Add to dashboard Cite

Receptor desensitization involving receptor phosphorylation and subsequent βArrestin (βArr) recruitment has been implicated in the tolerance development mediated by μ-opioid receptor (OPRM1). However, the roles of receptor phosphorylation and βArr on morphine-induced OPRM1 desensitization remain to be demonstrated. Using OPRM1-induced intracellular Ca 2+ ([Ca 2+ ] i ) release to monitor receptor activation, as predicted, [D-Ala 2 , N-Me-Phe 4 , Gly 5 -ol]-enkephalin (DAMGO), induced OPRM1 desensitization in a receptor phosphorylation-and βArr-dependent manner. The DAMGO-induced OPRM1 desensitization was attenuated significantly when phosphorylation deficient OPRM1 mutants or Mouse Embryonic Fibroblast (MEF) cells from βArr1 and 2 knockout mice were used in the studies. Specifically, DAMGO-induced desensitization was blunted in HEK293 cells expressing the OPRM1S375A mutant and was eliminated in MEF cells isolated from βArr2 knockout mice expressing the wild type OPRM1. However, although morphine also could induce a rapid desensitization on [Ca 2+ ] i release to a greater extent than that of DAMGO and could induce the phosphorylation of Ser 375 residue, morphine-induced desensitization was not influenced by mutating the phosphorylation sites or in MEF cells lacking βArr1 and 2. Hence, morphine could induce OPRM1 desensitization via pathway independent of βArr, thus suggesting the in vivo tolerance development to morphine can occur in the absence of βArr.

show abstract

“…It is known that the expression of Fas requires protein kinase C (PKC) and expression of FasL requires both PKC and cytosolic Ca 2ϩ (28). Because signaling through the MOR enhances cytosolic free Ca 2ϩ levels in human embryonic kidney 293 cells (29,30) and also induces PKC activation in the rat brain (31), it is possible that activation of PKC and cytosolic Ca 2ϩ release by morphine may lead to enhanced Fas and FasL expression during TCR activation. Interestingly, resting splenic T cells have also been shown to express ␦ opioid receptor (DOR) mRNA transcripts whose expression can be enhanced or inhibited depending upon the use of anti-CD3 or PMA and ionomycin, respectively, to stimulate T cells (32,33).…”

Section: Discussionmentioning

confidence: 99%

Chronic Morphine Treatment Promotes Specific Th2 Cytokine Production by Murine T Cells In Vitro via a Fas/Fas Ligand-Dependent Mechanism

Greeneltch

Kelly-Welch

Shi³

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Improper homeostasis of Th1 and Th2 cell differentiation can promote pathological immune responses such as autoimmunity and asthma. A number of factors govern the development of these cells including TCR ligation, costimulation, death effector expression, and activation-induced cell death (AICD). Although chronic morphine administration has been shown to selectively promote Th2 development in unpurified T cell populations, the direct effects of chronic morphine on Th cell skewing and cytokine production by CD4+ T cells have not been elucidated. We previously showed that morphine enhances Fas death receptor expression in a T cell hybridoma and human PBL. In addition, we have demonstrated a role for Fas, Fas ligand (FasL), and TRAIL in promoting Th2 development via killing of Th1 cells. Therefore, we analyzed whether the ability of morphine to affect Th2 cytokine production was mediated by regulation of Fas, FasL, and TRAIL expression and AICD directly in purified Th cells. We found that morphine significantly promoted IL-4 and IL-13 production but did not alter IL-5 or IFN-γ. Furthermore, morphine enhanced the mRNA expression of Fas, FasL and TRAIL and promoted Fas-mediated AICD of CD4+ T cells. Additionally, blockade of Fas/FasL interaction by anti-FasL inhibited the morphine-induced production of IL-4 and IL-13 and AICD of CD4+ T cells. These results suggest that morphine preferentially enhances Th2 cell differentiation via killing of Th1 cells in a Fas/FasL-dependent manner.

show abstract

Influence of chronic morphine treatment on protein kinase C activity: comparison with butorphanol and implication for opioid tolerance

Cited by 85 publications

References 20 publications

Up-Regulation of AGS3 during Morphine Withdrawal Promotes cAMP Superactivation via Adenylyl Cyclase 5 and 7 in Rat Nucleus Accumbens/Striatal Neurons

Up-Regulation of AGS3 during Morphine Withdrawal Promotes cAMP Superactivation via Adenylyl Cyclase 5 and 7 in Rat Nucleus Accumbens/Striatal Neurons

Morphine-induced μ-opioid receptor rapid desensitization is independent of receptor phosphorylation and β-arrestins

Chronic Morphine Treatment Promotes Specific Th2 Cytokine Production by Murine T Cells In Vitro via a Fas/Fas Ligand-Dependent Mechanism

Contact Info

Product

Resources

About