title: Bone marrow stromal and vascular smooth muscle cells have chemosensory capacity via bitter taste receptor expression.
abstract: The ability of cells to detect changes in the microenvironment is important in cell signaling and responsiveness to environmental fluctuations. Our interest is in understanding how human bone marrow stromal-derived cells (MSC) and their relatives, vascular smooth muscle cells (VSMC), interact with their environment through novel receptors. We found, through a proteomics screen, that MSC express the bitter taste receptor, TAS2R46, a protein more typically localized to the taste bud. Expression was also confirmed in VSMCs. A prototypical bitter compound that binds to the bitter taste receptor class, denatonium, increased intracellular calcium release and decreased cAMP levels as well as increased the extracellular release of ATP in human MSC. Denatonium also bound and activated rodent VSMC with a change in morphology upon compound exposure. Finally, rodents given denatonium in vivo had a significant drop in blood pressure indicating a vasodilator response. This is the first description of chemosensory detection by MSC and VSMCs via a taste receptor. These data open a new avenue of research into discovering novel compounds that operate through taste receptors expressed by cells in the marrow and vascular microenvironments.
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis, Minnesota, United States of America. lundx072@umn.edu
authors.forename: Troy C
authors.initials: TC
authors.lastname: Lund
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Kobs
authors.forename: Ashley
authors.initials: A
authors.lastname: Kramer
authors.forename: Mick
authors.initials: M
authors.lastname: Nyquist
authors.forename: Marcos T
authors.initials: MT
authors.lastname: Kuroki
authors.forename: John
authors.initials: J
authors.lastname: Osborn
authors.forename: Diane S
authors.initials: DS
authors.lastname: Lidke
authors.forename: Shalini T
authors.initials: ST
authors.lastname: Low-Nam
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D000098706:Taste Receptors, Type 2
chemical_list: D002118:Calcium; D000644:Quaternary Ammonium Compounds; D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; C043414:denatonium