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Related Concept Videos

Transducer Mechanism: G Protein–Coupled Receptors01:30

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G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
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G Protein-coupled Receptors01:15

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G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
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Activation and Inactivation of G Proteins01:22

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Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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Transducer Mechanism: Enzyme-Linked Receptors01:27

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Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
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G-Protein Gated Ion Channels01:21

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GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
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GPR84 in physiology-Many functions in many tissues.

Rubina Aktar1, Silvia Rondinelli1, Madusha Peiris1

  • 1Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

British Journal of Pharmacology
|August 3, 2023
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Summary

G protein-coupled receptor 84 (GPR84) is activated by fatty acids and plays roles in inflammation and nutrient sensing. Research explores its functions in metabolism and the gastrointestinal tract.

Keywords:
GPCRGPR84appetiteinflammation gastrointestinal tract (GIT)medium chain fatty acids (MCFAs)metabolism

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Area of Science:

  • Pharmacology
  • Gastroenterology
  • Metabolism

Background:

  • G protein-coupled receptors (GPCRs) are crucial drug targets.
  • GPR84 is an orphan receptor activated by medium-chain fatty acids and synthetic agonists.
  • Emerging evidence links GPR84 to inflammatory pathways and nutrient sensing.

Purpose of the Study:

  • To review the diverse physiological roles of GPR84.
  • To explore GPR84's pharmacology, localization, and expression.
  • To focus on GPR84's function in the gastrointestinal tract.

Main Methods:

  • Analysis of pre-clinical and clinical study data.
  • Review of literature on GPR84 pharmacology and function.
  • Investigation of nutrient-sensing mechanisms involving GPR84.

Main Results:

  • GPR84 is implicated in inflammatory responses.
  • GPR84 acts as a nutrient sensor, influencing energy metabolism and food intake.
  • Pre-clinical and clinical data reveal multiple roles for GPR84 across physiological systems.

Conclusions:

  • GPR84 is a multifaceted receptor with significant roles in inflammation and metabolism.
  • Further research into GPR84's functions, particularly in the gastrointestinal tract, is warranted.
  • GPR84 represents a promising therapeutic target for metabolic and inflammatory diseases.