Bitter taste receptors profiling in the human blood-cerebrospinal fluid-barrier

[Display omitted] 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). Ho...

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Published in:Biochemical pharmacology 2020-07, Vol.177, p.113954-113954, Article 113954
Main Authors: Duarte, Ana C., Santos, José, Costa, Ana R., Ferreira, Catarina L., Tomás, Joana, Quintela, Telma, Ishikawa, Hiroshi, Schwerk, Christian, Schroten, Horst, Ferrer, Isidro, Carro, Eva, Gonçalves, Isabel, Santos, Cecília R.A.
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Animals
Bitter taste receptors
Blood-Brain Barrier - metabolism
Blood-cerebrospinal fluid barrier
Cell Line, Tumor
Cerebrospinal Fluid - metabolism
Choroid plexus
Choroid Plexus - metabolism
Epithelial Cells - metabolism
Female
Gene Expression Profiling - methods
Humans
Male
Middle Aged
Rats
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
Receptors, G-Protein-Coupled - blood
Receptors, G-Protein-Coupled - genetics
Signal Transduction - genetics
Taste
Taste signalling
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Summary:[Display omitted] 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, PLCβ2 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.
ISSN:0006-2952
1873-2968
DOI:10.1016/j.bcp.2020.113954