%0 Journal Article
%A Apweiler, Matthias
%A Streyczek, Jana
%A Saliba, Soraya Wilke
%A Collado, Juan Antonio
%A Hurrle, Thomas
%A Graßle, Simone
%A Muñoz, Eduardo
%A Normann, Claus
%A Hellwig, Sabine
%A Brase, Stefan
%A Fiebich, Bernd L.
%T Functional Selectivity of Coumarin Derivates Acting via GPR55 in Neuroinflammation.
%D 2022
%U http://hdl.handle.net/10668/21133
%X 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.
%K GPR55
%K PGE2
%K SK-N-SH
%K Coumarin derivates
%K Functional selectivity
%K Neuroinflammation
%K Primary microglia
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