Journal
BIOCHEMICAL PHARMACOLOGY
Volume 177, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2020.113954
Keywords
Choroid plexus; Blood-cerebrospinal fluid barrier; Taste signalling; Bitter taste receptors
Categories
Funding
- Portuguese Foundation for Science and Technology (FCT, Portugal) [PTDC/SAU-NEU/114800/2009, UID/Multi/04326/2013, UID/Multi/00709/2013, UID/Multi/00709/2019]
- FEDER funds through the POCI - COMPETE 2020 - Operational Programme Competitiveness and Internationalization in Axis I Strengthening research, technological development and innovation [POCI-01-0145-FEDER-007491]
- Programa Operacional do Centro, Centro 2020 through the ICON project (Interdisciplinary Challenges On Neurodegeneration) [CENTRO-010145-FEDER-000013]
- Instituto de Salud Carlos III [PI18/00118]
- FEDER
- CIBERNED [PI2016/01]
- Comunidad de Madrid [S2017/BMD-3700]
- Structural Funds of the European Union
- [POCI01-0145-FEDER-022122]
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The choroid plexus (CP) epithelial cells establish an important blood-brain interface, the blood-cerebrospinal fluid barrier (BCSFB), which constitutes a complementary gateway to the blood-brain-barrier for the entrance of several molecules into the central nervous system (CNS). However, the mechanisms that operate at the BCSFB to regulate the molecular traffic are still poorly understood. The taste signalling machinery, present in many extra-oral tissues, is involved in the chemical sensing of the composition of body fluids. We have identified this pathway in rat CP and hypothesised that it could also be present in the human BCSFB. In this study, we characterised the bitter taste receptors (TAS2Rs) expression profiling in human CP by combining data retrieved from available databases of the human CP transcriptome with its expression analysis in a human CP cell line and immunohistochemistry of human CP sections from men and women. TAS2R4, 5, 14 and 39 expression was confirmed in human CP tissue by immunohistochemistry and in HIBCPP cells by RT-PCR, immunofluorescence and Western blot. Moreover, the presence of downstream effector proteins GNAT3, PLC beta 2 and TRPM5 was also detected in HIBCPP cells. Then, we demonstrated that HIBCPP cells respond to chloramphenicol via TAS2R39 and to quercetin via TAS2R14. Our findings support an active role of TAS2Rs at the human BCSFB, as surveyors of the bloodstream and CSF compositions. These findings open new avenues for studies on the uptake of relevant compounds for targeted therapies of the CNS.
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