scholarly journals How Oliceridine (TRV-130) Binds and Stabilizes a μ-Opioid Receptor Conformational State That Selectively Triggers G Protein Signaling Pathways

Biochemistry ◽  
2016 ◽  
Vol 55 (46) ◽  
pp. 6456-6466 ◽  
Author(s):  
Sebastian Schneider ◽  
Davide Provasi ◽  
Marta Filizola
Keyword(s):  
Signaling Pathways ◽  
G Protein ◽  
Opioid Receptor ◽  
Conformational State ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Μ Opioid Receptor

scholarly journals A G protein signaling-biased agonist at the μ-opioid receptor reverses morphine tolerance while preventing morphine withdrawal

2019 ◽  
Vol 45 (2) ◽  
pp. 416-425 ◽  
Author(s):  
Travis W. Grim ◽  
Cullen L. Schmid ◽  
Edward L. Stahl ◽  
Fani Pantouli ◽  
Jo-Hao Ho ◽  
...  
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Morphine Tolerance ◽  
Morphine Withdrawal ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Μ Opioid Receptor ◽  
Biased Agonist

scholarly journals Oxytocin Is a Positive Allosteric Modulator of κ-Opioid Receptors but Not δ-Opioid Receptors in the G Protein Signaling Pathway

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2651
Author(s):  
Kanako Miyano ◽  
Yuki Yoshida ◽  
Shigeto Hirayama ◽  
Hideki Takahashi ◽  
Haruka Ono ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
G Protein ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Allosteric Modulator ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Positive Allosteric Modulator ◽  
Dynorphin A ◽  
Opioid Signaling

Oxytocin (OT) influences various physiological functions such as uterine contractions, maternal/social behavior, and analgesia. Opioid signaling pathways are involved in one of the analgesic mechanisms of OT. We previously showed that OT acts as a positive allosteric modulator (PAM) and enhances μ-opioid receptor (MOR) activity. In this study, which focused on other opioid receptor (OR) subtypes, we investigated whether OT influences opioid signaling pathways as a PAM for δ-OR (DOR) or κ-OR (KOR) using human embryonic kidney-293 cells expressing human DOR or KOR, respectively. The CellKeyTM results showed that OT enhanced impedance induced by endogenous/exogenous KOR agonists on KOR-expressing cells. OT did not affect DOR activity induced by endogenous/exogenous DOR agonists. OT potentiated the KOR agonist-induced Gi/o protein-mediated decrease in intracellular cAMP, but did not affect the increase in KOR internalization caused by the KOR agonists dynorphin A and (-)-U-50488 hydrochloride (U50488). OT did not bind to KOR orthosteric binding sites and did not affect the binding affinities of dynorphin A and U50488 for KOR. These results suggest that OT is a PAM of KOR and MOR and enhances G protein signaling without affecting β-arrestin signaling. Thus, OT has potential as a specific signaling-biased PAM of KOR.

μ-Opioid receptor down-regulation and tolerance are not equally dependent upon G-protein signaling

2002 ◽  
Vol 72 (1-2) ◽  
pp. 273-278 ◽  
Author(s):  
Benedict A. Gomes ◽  
Ji Shen ◽  
Kristi Stafford ◽  
Minesh Patel ◽  
Byron C. Yoburn
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Down Regulation ◽  
Μ Opioid Receptor

scholarly journals Endogenous modification of the chemoattractant CXCL5 alters receptor usage and enhances its activity toward neutrophils and monocytes

2021 ◽  
Vol 14 (673) ◽  
pp. eaax3053
Author(s):  
Mieke Metzemaekers ◽  
Anneleen Mortier ◽  
Alessandro Vacchini ◽  
Daiane Boff ◽  
Karen Yu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
G Protein ◽  
Chemotactic Activity ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Agonist Activity ◽  
N Terminus ◽  
G Protein Coupled

The inflammatory human chemokine CXCL5 interacts with the G protein–coupled receptor CXCR2 to induce chemotaxis and activation of neutrophils. CXCL5 also has weak agonist activity toward CXCR1. The N-terminus of CXCL5 can be modified by proteolytic cleavage or deimination of Arg9 to citrulline (Cit), and these modifications can occur separately or together. Here, we chemically synthesized native CXCL5(1–78), truncated CXCL5 [CXCL5(9–78)], and the citrullinated (Cit9) versions and characterized their functions in vitro and in vivo. Compared with full-length CXCL5, N-terminal truncation resulted in enhanced potency to induce G protein signaling and β-arrestin recruitment through CXCR2, increased CXCL5-initiated internalization of CXCR2, and greater Ca2+ signaling downstream of not only CXCR2 but also CXCR1. Citrullination did not affect the capacity of CXCL5 to activate classical or alternative signaling pathways. Administering the various CXCL5 forms to mice revealed that in addition to neutrophils, CXCL5 exerted chemotactic activity toward monocytes and that this activity was increased by N-terminal truncation. These findings were confirmed by in vitro chemotaxis and Ca2+ signaling assays with primary human CD14+ monocytes and human THP-1 monocytes. In vitro and in vivo analyses suggested that CXCL5 targeted monocytes through CXCR1 and CXCR2. Thus, truncation of the N-terminus makes CXCL5 a more potent chemoattractant for both neutrophils and monocytes that acts through CXCR1 and CXCR2.

scholarly journals Light control of G protein signaling pathways by a novel photopigment

PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0205015
Author(s):  
Tomás Osorno ◽  
Oscar Arenas ◽  
Nelson J. Ramírez-Suarez ◽  
Fabio A. Echeverry ◽  
María del Pilar Gomez ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
G Protein ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Light Control
Sign in / Sign up

Export Citation Format

Share Document