Functional expression of adrenoreceptors in mesenchymal stromal cells derived from the human adipose tissue.
Cultured mesenchymal stromal cells (MSCs) from different sources represent a heterogeneous population of proliferating non-differentiated cells that contains multipotent stem cells capable of originating a variety of mesenchymal cell lineages. Despite tremendous progress in MSC biology spurred by their therapeutic potential, current knowledge on receptor and signaling systems of MSCs is mediocre. Here we isolated MSCs from the human adipose tissue and assayed their responsivity to GPCR agonists with Ca(2+) imaging. As a whole, a MSC population exhibited functional heterogeneity. Although a variety of first messengers was capable of stimulating Ca(2+) signaling in MSCs, only a relatively small group of cells was specifically responsive to the particular GPCR agonist, including noradrenaline. RT-PCR and immunocytochemistry revealed expression of α1B-, α2A-, and β2-adrenoreceptors in MSCs. Their sensitivity to subtype-specific adrenergic agonists/antagonists and certain inhibitors of Ca(2+) signaling indicated that largely the α2A-isoform coupled to PLC endowed MSCs with sensitivity to noradrenaline. The all-or-nothing dose-dependence was characteristic of responsivity of robust adrenergic MSCs. Noradrenaline never elicited small or intermediate responses but initiated large and quite similar Ca(2+) transients at all concentrations above the threshold. The inhibitory analysis and Ca(2+) uncaging implicated Ca(2+)-induced Ca(2+) release (CICR) in shaping Ca(2+) signals elicited by noradrenaline. Evidence favored IP3 receptors as predominantly responsible for CICR. Based on the overall findings, we inferred that adrenergic transduction in MSCs includes two fundamentally different stages: noradrenaline initially triggers a local and relatively small Ca(2+) signal, which next stimulates CICR, thereby being converted into a global Ca(2+) signal.
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
Polina D
PD
Kotova
Department of Biochemistry and Molecular Medicine, Faculty of Basic Medicine, Lomonosov Moscow State University, Russia.
Veronika Yu
VY
Sysoeva
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
Olga A
OA
Rogachevskaja
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
Marina F
MF
Bystrova
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
Alisa S
AS
Kolesnikova
Department of Biochemistry and Molecular Medicine, Faculty of Basic Medicine, Lomonosov Moscow State University, Russia.
Pyotr A
PA
Tyurin-Kuzmin
Department of Biochemistry and Molecular Medicine, Faculty of Basic Medicine, Lomonosov Moscow State University, Russia.
Julia I
JI
Fadeeva
Department of Biochemistry and Molecular Medicine, Faculty of Basic Medicine, Lomonosov Moscow State University, Russia.
Vsevolod A
VA
Tkachuk
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia. Electronic address: staskolesnikov@yahoo.com.
Stanislav S
SS
Kolesnikov
D000273:Adipose Tissue / Q000166:cytology*; D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000328:Adult; D002118:Calcium / Q000378:metabolism; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D008954:Models, Biological; D009638:Norepinephrine / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010716:Phosphatidylinositols; D011941:Receptors, Adrenergic; D002118:Calcium; D009638:Norepinephrine
Adrenergic receptor; Ca(2+) uncaging; Calcium-induced calcium release; IP(3) receptor; Mesenchymal stromal cell