The GBeta5 subunit that associates with the R7 subfamily of RGS proteins regulates mu-opioid effects

Sánchez‐Blázquez, Pilar; Rodríguez‐Díaz, Marta; López-Fando, Almudena; Rodríguez-Muñoz, María; Garzón, Javier

doi:10.1016/s0028-3908(03)00149-7

Cited by 40 publications

(63 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consequently, the downregulation of members of the neural R7 subfamily of RGS proteins (RGS6, RGS7, RGS9-2, and RGS11), or of the associated Gb5 protein, reduces m-opioid tachyphylaxis Sánchez-Blázquez et al, 2003). This is also observed after impairment of RGSZ1, and to a minor extent after impairment of GAIP (present work).…”

Section: Discussionsupporting

confidence: 53%

“…Interestingly, R7 or b5 knockdown mice show no acute tolerance to morphine Sánchez-Blázquez et al, 2003), although this does develop in RGSZ1, GAIP, and GIPC knockdown mice (present work). Thus, the interesting phenomena of opioid tachyphylaxis and acute tolerance can apparently be modulated in different ways.…”

Section: Discussionsupporting

confidence: 46%

“…Previous CNS studies have demonstrated the suitability of antisense oligodeoxynucleotides (ODNs) directed towards the mRNA for promoting downregulation of Ga subunits and RGS proteins (see eg, Garzón et al, 2000. This approach revealed a role for R4 and R7 proteins in the regulation of m and d receptor-mediated antinociception in mice Garzón et al, 2003;Sánchez-Blázquez et al, 2003). The R7 proteins facilitate the onset of tachyphylaxis during the time course of agonist effects as well as the development of tolerance to a single and adequate dose of agonists at m-opioid receptors Sánchez-Blázquez et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…This approach revealed a role for R4 and R7 proteins in the regulation of m and d receptor-mediated antinociception in mice Garzón et al, 2003;Sánchez-Blázquez et al, 2003). The R7 proteins facilitate the onset of tachyphylaxis during the time course of agonist effects as well as the development of tolerance to a single and adequate dose of agonists at m-opioid receptors Sánchez-Blázquez et al, 2003). The present work addresses the role of the RGS proteins of the Rz subfamily and of GIPC on the activity of agonists at m and d receptors.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

RGSZ1 and GAIP Regulate μ- but Not δ-Opioid Receptors in Mouse CNS: Role in Tachyphylaxis and Acute Tolerance

Garzón

Rodríguez-Muñoz

López-Fando

et al. 2004

Neuropsychopharmacol

105

View full text Add to dashboard Cite

In the CNS, the regulators of G-protein signaling (RGS) proteins belonging to the Rz subfamily, RGS19 (Ga interacting protein (GAIP)) and RGS20 (Z1), control the activity of opioid agonists at m but not at d receptors. Rz proteins show high selectivity in deactivating Gaz-GTP subunits. After reducing the expression of RGSZ1 with antisense oligodeoxynucleotides ( Knockdown of GAIP and of the GAIP interacting protein C-terminus (GIPC) led to changes in agonist effects at m but not at d receptors. The impairment of RGSZ1 extended the duration of morphine analgesia by at least 1 h beyond that observed in control animals. CTOP (Cys 2 , Tyr 3 , Orn 5 , Pen 7 -amide) antagonized morphine analgesia when given during the period in which the effect of morphine was enhanced by RGSZ1 knockdown. Thus, in naive mice, morphine tachyphylaxis originated in the presence of the opioid agonist and during the analgesia time course. The knockdown of RGSZ1 facilitated the development of tolerance to a single dose of morphine and accelerated tolerance to continuous delivery of the opioid. These results indicate that m but not d receptors are linked to Rz regulation. The m receptor-mediated activation of Gz proteins is effective at recruiting the adaptive mechanisms leading to the development of opioid desensitization.

show abstract

Section: Discussionsupporting

confidence: 53%

Section: Discussionsupporting

confidence: 46%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

RGSZ1 and GAIP Regulate μ- but Not δ-Opioid Receptors in Mouse CNS: Role in Tachyphylaxis and Acute Tolerance

Garzón

Rodríguez-Muñoz

López-Fando

et al. 2004

Neuropsychopharmacol

105

View full text Add to dashboard Cite

show abstract

“…The GAP activities of the RGS6/b5 and RGS11/b5 complexes also appear specific for Goa-GTP (Snow et al, 1998;Posner et al, 1999). However, R7 proteins have been shown to bind to activated Goa, Gi3a, and Gza subunits in rat and mouse brain membrane fractions (Saitoh et al, 1999: Rose et al, 2000Sánchez-Blázquez et al, 2003). It is therefore possible that to show GAP activity on Ga-GTP subunitsFdistinct from GoaFR7/b5 complexes require the assistance of as yet unidentified auxiliary proteins.…”

Section: Discussionmentioning

confidence: 99%

The R7 Subfamily of RGS Proteins Assists Tachyphylaxis and Acute Tolerance at μ-Opioid Receptors

Garzón

López-Fando

Sánchez‐Blázquez

2003

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

RGS proteins as targets in the treatment of intestinal inflammation and visceral pain: New insights and future perspectives

Sałaga

Storr²,

Martemyanov

et al. 2016

BioEssays

View full text Add to dashboard Cite

Regulators of G protein signalling (RGS) proteins provide timely termination of G protein-coupled receptor (GPCR) responses. Serving as a central control point in GPCR signalling cascades, RGS proteins are promising targets for drug development. In this review we discuss the involvement of RGS proteins in the pathophysiology of the gastrointestinal inflammation and their potential to become a target for anti-inflammatory drugs. Specifically, we evaluate the emerging evidence for modulation of selected receptor families: opioid, cannabinoid and serotonin by RGS proteins. We discuss how the regulation of RGS protein level and activity may modulate immunological pathways involved in the development of intestinal inflammation. Finally, we propose that RGS proteins may serve as a prognostic factor for survival rate in colorectal cancer. The ideas introduced in this review set a novel conceptual framework for the utilization of RGS proteins in the treatment of gastrointestinal inflammation, a growing major concern worldwide.

show abstract

The GBeta5 subunit that associates with the R7 subfamily of RGS proteins regulates mu-opioid effects

Cited by 40 publications

References 52 publications

RGSZ1 and GAIP Regulate μ- but Not δ-Opioid Receptors in Mouse CNS: Role in Tachyphylaxis and Acute Tolerance

RGSZ1 and GAIP Regulate μ- but Not δ-Opioid Receptors in Mouse CNS: Role in Tachyphylaxis and Acute Tolerance

The R7 Subfamily of RGS Proteins Assists Tachyphylaxis and Acute Tolerance at μ-Opioid Receptors

RGS proteins as targets in the treatment of intestinal inflammation and visceral pain: New insights and future perspectives

Contact Info

Product

Resources

About