Back to Search
Start Over
The C3a receptor antagonist SB 290157 has agonist activity
- Source :
- Immunology letters. 100(2)
- Publication Year :
- 2005
-
Abstract
- The anaphylatoxin C3a is an important immune regulator with a number of distinct functions in both innate and adaptive immunity. Many of these roles have been ascribed to C3a based on studies in mice genetically modified to lack its precursor, C3, or its receptor, C3aR. However, other presumed functions of C3a are based on results obtained with a recently described small molecule ligand of C3aR, SB 290157. Although this compound was originally described as an antagonist and appears to act as such in some systems, it has recently been shown to have effects that cannot be explained by simple antagonism of C3aR. In the current study, SB 290157 is shown to have full agonist activity on C3aR in a variety of cell systems, including a calcium mobilization assay in transfected RBL cells, a β-lactamase assay in CHO-NFAT-bla-Gα16 cells and an enzyme-release assay in differentiated U-937 cells. On the other hand, the compound lacks agonist activity in guinea pig platelets, cells known to express C3aR at very low levels. SB 290157 agonism of C3aR is consistent with recent discrepant data obtained using this molecule. These results caution against attributing novel roles to C3a based on data obtained with SB 290157 and highlight a continuing need for the identification of true small molecule C3aR antagonists.
- Subjects :
- Agonist
Blood Platelets
medicine.drug_class
Immunology
CHO Cells
Biology
Arginine
Transfection
Binding, Competitive
beta-Lactamases
Cricetulus
Cell Line, Tumor
Cricetinae
medicine
Immunology and Allergy
Animals
Humans
Anaphylatoxin
Benzhydryl Compounds
Receptor
G protein-coupled receptor
Dose-Response Relationship, Drug
Cell Membrane
Membrane Proteins
U937 Cells
Acquired immune system
Small molecule
Rats
Receptors, Complement
Macaca fascicularis
Biochemistry
biology.protein
Complement C3a
Calcium
C3a receptor
Subjects
Details
- ISSN :
- 01652478
- Volume :
- 100
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Immunology letters
- Accession number :
- edsair.doi.dedup.....a7d7693d91f27c37eab2a646f3da923e