Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Nicotinic acid receptor agonists differentially activate downstream effectors.

Jeremy G Richman1, Martha Kanemitsu-Parks1, Ibragim Gaidarov1

  • 1Arena Pharmaceuticals, Inc., San Diego, California 92121.

The Journal of Biological Chemistry
|April 25, 2007
PubMed
Summary

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Diazepine Agonists of the 5-HT<sub>2C</sub> Receptor with Unprecedented Selectivity: Discovery of Bexicaserin (LP352).

Journal of medicinal chemistry·2025
Same author

Interactions between corticotropin releasing factor signaling and prophylactic antibiotics on measures of intestinal function in weaned and transported pigs.

Frontiers in physiology·2023
Same author

Novel (R)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines as potent and selective agonists of the 5-HT<sub>2C</sub> receptor.

Bioorganic & medicinal chemistry letters·2021
Same author

Discovery of a lead series of potent benzodiazepine 5-HT<sub>2C</sub> receptor agonists with high selectivity in functional and binding assays.

Bioorganic & medicinal chemistry letters·2020
Same author

Angiotensin (1-7) does not interact directly with MAS1, but can potently antagonize signaling from the AT1 receptor.

Cellular signalling·2018
Same author

Embelin and its derivatives unravel the signaling, proinflammatory and antiatherogenic properties of GPR84 receptor.

Pharmacological research·2018
Same journal

Wanted and unwanted modifications of mRNA, and their effect on gene expression and signaling.

The Journal of biological chemistry·2026
Same journal

TGF-β2 drives lipid droplet accumulation in chondrocytes through the TβRI/p-Smad3/Fabp5 axis.

The Journal of biological chemistry·2026
Same journal

Macrophage-specific targeting of histone demethylases with small-molecule inhibitors suppresses inflammatory response in vivo.

The Journal of biological chemistry·2026
Same journal

Substrate and target selectivity of 4'-fluoroadenosine against viral and host polymerases.

The Journal of biological chemistry·2026
Same journal

Correction: Characterization of Mast2 kinase defines structural features, regulation, and substrates.

The Journal of biological chemistry·2026
Same journal

Isotope-Edited ESEEM: A New Method for Probing Copper Binding Sites in Neurodegenerative Proteins.

The Journal of biological chemistry·2026
See all related articles
This summary is machine-generated.

New GPR109A pyrazole agonists effectively lower cholesterol by inhibiting lipolysis without causing flushing. These compounds offer a promising alternative to nicotinic acid for atherosclerosis treatment.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Cardiovascular Research

Background:

  • Nicotinic acid is effective for atherosclerosis but limited by flushing.
  • Its therapeutic effects are mediated by GPR109A, a receptor on adipocytes and immune cells.
  • Flushing is linked to prostaglandin D2 release from skin Langerhans cells.

Purpose of the Study:

  • To find GPR109A agonists that selectively activate anti-lipolytic pathways.
  • To develop treatments that avoid the flushing side effect of nicotinic acid.

Main Methods:

  • Identified and tested GPR109A pyrazole agonists.
  • Evaluated inhibition of lipolysis in vitro and in vivo.
  • Assessed flushing response and prostaglandin D2 release in vivo.
  • Monitored GPR109A receptor internalization and ERK 1/2 phosphorylation.

Related Experiment Videos

Main Results:

  • Pyrazole agonists fully inhibited lipolysis both in vitro and in vivo.
  • These agonists did not elicit flushing and antagonized nicotinic acid-induced flushing.
  • Non-flushing agonists did not cause GPR109A internalization or ERK 1/2 phosphorylation.

Conclusions:

  • Distinct signaling pathways mediate GPR109A's anti-lipolytic and flushing effects.
  • Selective GPR109A agonists can inhibit lipolysis without causing flushing.
  • These findings pave the way for improved atherosclerosis therapies.