Apweiler, MatthiasStreyczek, JanaSaliba, Soraya WilkeCollado, Juan AntonioHurrle, ThomasGraßle, SimoneMuñoz, EduardoNormann, ClausHellwig, SabineBrase, StefanFiebich, Bernd L.2023-05-032023-05-032022-06-13Apweiler 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):959http://hdl.handle.net/10668/21133Anti-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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/GPR55PGE2SK-N-SHCoumarin derivatesFunctional selectivityNeuroinflammationPrimary microgliaAnimalsAnti-Inflammatory AgentsCell LineCell ProliferationCell SurvivalCells, CulturedCoumarinsDinoprostoneHumansMiceMicrogliaNeuronsOrgan SpecificityPrimary Cell CultureReceptors, Cannabinoidresearch article35055142open accessAntiinflamatoriosCultivo primario de celulasEspecificidad de organosMicrogliaProliferacion celularReceptores de cannabinoidesSupervivencia celularDinoprostona10.3390/ijms230209591422-0067PMC8779649https://www.mdpi.com/1422-0067/23/2/959/pdf?version=1642324664https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779649/pdf