Regulator of G protein signaling proteins differentially modulate signaling of μ and δ opioid receptors

Xie, Zhihua; Li, Zhisong; Guo, Lei; Ye, Caiying; Li, Juan; Yu, Xiaoli; Yang, Huifen; Wang, Yulin; Chen, Chongguang; Zhang, Dechang; Liu‐Chen, Lee‐Yuan

doi:10.1016/j.ejphar.2007.03.005

Cited by 28 publications

(37 citation statements)

References 31 publications

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“…Cells were grown in DMEM supplemented with fetal bovine serum (10%), penicillin (100 U/ml), streptomycin (100 g/ml), and nonessential amino acids (0.1 mM) at 5% CO 2 and 37°C, and G-418 (Geneticin) was used for selection or maintenance of selection of stable cell lines. Calcium phosphate transfection was performed as described elsewhere (Xie et al, 2005(Xie et al, , 2007a to introduce the receptor and/or transporter into different cells for assays. For cotransfection, the ratio of constructs and the amount of total DNA were held constant with pcDNA3.1.…”

Section: Methodsmentioning

confidence: 99%

A Receptor Mechanism for Methamphetamine Action in Dopamine Transporter Regulation in Brain

Xie

Miller²

2009

J Pharmacol Exp Ther

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This study reveals a novel receptor mechanism for methamphetamine action in dopamine transporter (DAT) regulation. Trace amine-associated receptor 1 (TAAR1) is expressed in brain dopaminergic nuclei and is activated by methamphetamine in vitro. Here, we show that methamphetamine interaction with TAAR1 3 H]dopamine (10 nM) in a TAAR1-dependent manner. In DAT biotinylation assays using the same cell and synaptosome preparations, we observed that 1 M methamphetamine induced DAT internalization in a TAAR1-dependent manner. All these TAAR1-mediated effects of methamphetamine were blocked by the protein kinase inhibitors H89 [N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline] and/or 2-{8-[(dimethylamino) methyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-3-yl}-3-(1-methylindol-3-yl)maleimide (Ro32-0432), suggesting that methamphetamine interaction with TAAR1 triggers cellular phosphorylation cascades and leads to the observed effects of methamphetamine on DAT. These findings demonstrate a mediatory role of TAAR1 in methamphetamine action in DAT regulation and implicate this receptor as a potential target of therapeutics drugs for methamphetamine addiction.

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Section: Methodsmentioning

confidence: 99%

A Receptor Mechanism for Methamphetamine Action in Dopamine Transporter Regulation in Brain

Xie

Miller²

2009

J Pharmacol Exp Ther

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“…Cells were grown in DMEM supplemented with fetal bovine serum (10%), penicillin (100 U/ml), streptomycin (100 g/ml), and nonessential amino acids (0.1 mM) at 5% CO 2 and 37°C, and G418 was used for selection or maintenance of selection of stable cell lines. Calcium phosphate transfection was performed as described elsewhere (Xie et al, 2005(Xie et al, , 2007a to introduce the necessary receptor and transporter into different cells for assays. For cotransfection, the ratio of constructs and the amount of total DNA was held constant with pcDNA3.1.…”

Section: Methodsmentioning

confidence: 99%

Modulation of Monoamine Transporters by Common Biogenic Amines via Trace Amine-Associated Receptor 1 and Monoamine Autoreceptors in Human Embryonic Kidney 293 Cells and Brain Synaptosomes

Xie¹,

Westmoreland²,

Miller³

2008

J Pharmacol Exp Ther

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In brain monoaminergic systems, common biogenic amines, including dopamine, norepinephrine, and serotonin, serve as neurotransmitters. Monoamine autoreceptors provide feedback regulation in neurotransmitter release, and monoamine transporters clear the released neurotransmitters to control synaptic signaling. Recently, trace amine-associated receptor 1 (TAAR1) has been found to be expressed in brain monoaminergic nuclei and activated by common biogenic amines in vitro. This study used transfected cells and brain synaptosomes to evaluate the interaction of common biogenic amines with TAAR1 and monoamine autoreceptors and explore their modulatory effects on monoamine transporters. We confirmed that TAAR1 was activated by dopamine, norepinephrine, and serotonin and demonstrated that TAAR1 signaling was attenuated by monoamine autoreceptors at exposure to dopamine, norepinephrine, and serotonin. In transfected cells, TAAR1 in response to dopamine, norepinephrine, and serotonin significantly inhibited uptake and promoted efflux of H]serotonin, respectively, when the monoamine autoreceptors were blocked. By comparing the effects of dopamine, norepinephrine, and serotonin in monkey and wild-type mouse synaptosomes to their effects in TAAR1 knockout mouse synaptosomes, we deduced that TAAR1 activity inhibited uptake and promoted efflux by monoamine transporters and that monoamine autoreceptors exerted opposite effects. These data provide the first evidence that common biogenic amines modulate monoamine transporter function via both TAAR1 and monoamine autoreceptors, which may balance monoaminergic activity.Common biogenic amines are neurotransmitters in brain that are synthesized and packaged in monoaminergic neurons and released into synaptic clefts to interact with presynaptic and postsynaptic receptors. Monoamine transporters, including dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT), clear the released neurotransmitters to terminate neural signaling (Uhl and Johnson, 1994;Masson et al., 1999) and are functionally or dynamically regulated by various chemicals, including psychostimulants and antidepressants (Sulzer et al., 1995;Gutman and Owens, 2006;Fleckenstein et al., 2007). Aberrant transport of common biogenic amines by monoamine transporters in brain is associated with a variety of neuropsychiatric disorders/diseases, such as anxiety, depression, Parkinson's disease, schizophrenia, suicide, and drug abuse/addiction (Klimek et al., 1997;Arango et al., 2002;Schmitt et al., 2006;Serretti et al., 2006). Monoamine autoreceptors, residing on the presynaptic membranes of monoaminergic neurons, monitor and respond to the released common biogenic amines to provide feedback regulation of Article, publication date, and citation information can be found at http://jpet.aspetjournals.org. doi:10.1124/jpet.107.135079. ABBREVIATIONS:DAT, dopamine transporter; 5-HT 1A and 5-HT 1B , subtype A and B of serotonin receptor 1; ␣ 2A and ␣ 2B , subtype A and B of alpha adrenal rec...

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“…For example, as noted already, endogenous RGS4 does not act as a GAP for endogenous MOR signaling in SH-SY5Y cells (Wang et al, 2009) and the RGS4 knockout mouse shows only very minor phenotypic responses to morphine (Grillet et al, 2005;Han et al, 2010). On the other hand, RGS4 has been reported to act negatively to modulate MOR signaling in various heterologous systems (Ippolito et al, 2002;Garnier et al, 2003;Xie et al, 2005;Georgoussi et al, 2006;Xie et al, 2007;Talbot et al, 2010). NOPR couples to Gai/o proteins and so is expected to be sensitive to the GAP activity of RGS proteins (Xie et al, 2005).…”

Section: Rgs19 Modulates M-opioid Receptor Signalingmentioning

confidence: 99%

“…Thus, the apparent selectivity of RGS19 as a GAP for MOR signaling and RGS4 as a GAP for DOR signaling is unexpected. However, there is accumulating evidence for GPCRs contributing to the specificity of RGS protein action (Xu et al, 1999;Saitoh et al, 2002;Wang et al, 2002Wang et al, , 2009Bernstein et al, 2004), and we (Wang et al, 2009) and others (Georgoussi et al, 2006;Xie et al, 2007) have suggested a role for the C-terminus of opioid receptors in providing specificity of RGS action at DOR versus MOR. Moroever, outside the RH domain, RGS19 has a more complex structure than RGS4 with an N-terminal cysteine string that binds to the N-terminal leucine-rich region of GAIP-interacting protein N-terminus (Fischer et al, Fig.…”

Section: Rgs19 Modulates M-opioid Receptor Signalingmentioning

confidence: 99%

“…RGS19 does not show significant GAP activity toward Gai/o proteins involved in MOR signaling in COS-7 cells (Xie et al, 2005), yet it increases the ability of the MOR agonist D-Ala, N-Me-Phe, Gly-ol 5 -enkephalin (DAMGO) to inhibit adenylyl cyclase (AC) in human embryonic kidney (HEK) 293 cells (Xie et al, 2007) and modulates the antinociceptive actions of morphine and DAMGO in mice (Garzon et al, 2004). RGS19 does not act as a GAP for DOR-coupled Gai/o proteins in HEK293 (Xie at al., 2007) or in COS-7 cells (Xie et al, 2005). In addition, antisense knockdown of RGS19 or its binding partner GIPC does not alter DOR agonist-mediated antinociceptive behavior in mice (Garzon et al, 2004).…”

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confidence: 99%

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Modulation of μ-Opioid Receptor Signaling by RGS19 in SH-SY5Y Cells

Wang

Traynor

2012

Mol Pharmacol

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Regulator of G-protein signaling protein 19 (RGS19), also known as Ga-interacting protein (GAIP), acts as a GTPase accelerating protein for Gaz as well as Gai/o subunits. Interactions with GAIP-interacting protein N-terminus and GAIP-interacting protein C-terminus (GIPC) link RGS19 to a variety of intracellular proteins. Here we show that RGS19 is abundantly expressed in human neuroblastoma SH-SY5Y cells that also express mand d-opioid receptors (MORs and DORs, respectively) and nociceptin receptors (NOPRs). Lentiviral delivery of short hairpin RNA specifically targeted to RGS19 reduced RGS19 protein levels by 69%, with a similar reduction in GIPC. In RGS19-depleted cells, there was an increase in the ability of 5 -enkephalin or SNC80) agonists increased RGS19 and GIPC protein levels in a time-and concentration-dependent manner. The MOR-induced increase in RGS19 protein was prevented by pretreatment with pertussis toxin or the opioid antagonist naloxone. Protein kinase C (PKC) activation alone increased the level of RGS19 and inhibitors of PKC 5,6,7,13-tetrahydro-13-methyl-5-oxo-12H-indolo [2,3-a] pyrrolo [3,4-c]carbazole-12-propanenitrile and mitogen-activated protein kinase kinase 1 2-(2-amino-3-methoxyphenyl)-4H-chromen-4-one, but not protein kinase A (H89), completely blocked DAMGO-induced RGS19 protein accumulation. The findings show that RGS19 and GIPC are jointly regulated, that RGS19 is a GTPase accelerating protein for MOR with selectivity over DOR and NOPR, and that chronic MOR or DOR agonist treatment increases RGS19 levels by a PKC and the MAPK pathway-dependent mechanism.

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Regulator of G protein signaling proteins differentially modulate signaling of μ and δ opioid receptors

Cited by 28 publications

References 31 publications

A Receptor Mechanism for Methamphetamine Action in Dopamine Transporter Regulation in Brain

A Receptor Mechanism for Methamphetamine Action in Dopamine Transporter Regulation in Brain

Modulation of Monoamine Transporters by Common Biogenic Amines via Trace Amine-Associated Receptor 1 and Monoamine Autoreceptors in Human Embryonic Kidney 293 Cells and Brain Synaptosomes

Modulation of μ-Opioid Receptor Signaling by RGS19 in SH-SY5Y Cells

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