RT Journal Article
T1 Functional Selectivity of Coumarin Derivates Acting via GPR55 in Neuroinflammation.
A1 Apweiler, Matthias
A1 Streyczek, Jana
A1 Saliba, Soraya Wilke
A1 Collado, Juan Antonio
A1 Hurrle, Thomas
A1 Graßle, Simone
A1 Muñoz, Eduardo
A1 Normann, Claus
A1 Hellwig, Sabine
A1 Brase, Stefan
A1 Fiebich, Bernd L.
K1 GPR55
K1 PGE2
K1 SK-N-SH
K1 Coumarin derivates
K1 Functional selectivity
K1 Neuroinflammation
K1 Primary microglia
AB Anti-neuroinflammatory treatment has gained importance in the search for pharmacological treatments of different neurological and psychiatric diseases, such as depression, schizophrenia, Parkinson's disease, and Alzheimer's disease. Clinical studies demonstrate a reduction of the mentioned diseases' symptoms after the administration of anti-inflammatory drugs. Novel coumarin derivates have been shown to elicit anti-neuroinflammatory effects via G-protein coupled receptor GPR55, with possibly reduced side-effects compared to the known anti-inflammatory drugs. In this study, we, therefore, evaluated the anti-inflammatory capacities of the two novel coumarin-based compounds, KIT C and KIT H, in human neuroblastoma cells and primary murine microglia. Both compounds reduced PGE2-concentrations likely via the inhibition of COX-2 synthesis in SK-N-SH cells but only KIT C decreased PGE2-levels in primary microglia. The examination of other pro- and anti-inflammatory parameters showed varying effects of both compounds. Therefore, the differences in the effects of KIT C and KIT H might be explained by functional selectivity as well as tissue- or cell-dependent expression and signal pathways coupled to GPR55. Understanding the role of chemical residues in functional selectivity and specific cell- and tissue-targeting might open new therapeutic options in pharmacological drug development and might improve the treatment of the mentioned diseases by intervening in an early step of their pathogenesis.
PB MDPI
YR 2022
FD 2022-06-13
LK http://hdl.handle.net/10668/21133
UL http://hdl.handle.net/10668/21133
LA en
NO Apweiler M, Streyczek J, Saliba SW, Collado JA, Hurrle T, Gräßle S, et al. Functional Selectivity of Coumarin Derivates Acting via GPR55 in Neuroinflammation. Int J Mol Sci. 2022 Jan 16;23(2):959
DS RISalud
RD Apr 5, 2025