Activation of β-adrenergic receptors is required for elevated α1A-adrenoreceptors expression and signaling in mesenchymal stromal cells.
Sympathetic neurons are important components of mesenchymal stem cells (MSCs) niche and noradrenaline regulates biological activities of these cells. Here we examined the mechanisms of regulation of MSCs responsiveness to noradrenaline. Using flow cytometry, we demonstrated that α1A adrenergic receptors isoform was the most abundant in adipose tissue-derived MSCs. Using calcium imaging in single cells, we demonstrated that only 6.9 ± 0.8% of MSCs responded to noradrenaline by intracellular calcium release. Noradrenaline increases MSCs sensitivity to catecholamines in a transitory mode. Within 6 hrs after incubation with noradrenaline the proportion of cells responding by Ca(2+) release to the fresh noradrenaline addition has doubled but declined to the baseline after 24 hrs. Increased sensitivity was due to the elevated quantities of α1A-adrenergic receptors on MSCs. Such elevation depended on the stimulation of β-adrenergic receptors and adenylate cyclase activation. The data for the first time clarify mechanisms of regulation of MSCs sensitivity to noradrenaline.
Department of Biochemistry and Molecular Medicine, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow, Russia.
Pyotr A
PA
Tyurin-Kuzmin
Department of Biochemistry and Molecular Medicine, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow, Russia.
Julia I
JI
Fadeeva
Department of Biochemistry and Molecular Medicine, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow, Russia.
Margarita A
MA
Kanareikina
Department of Biochemistry and Molecular Medicine, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow, Russia.
Natalia I
NI
Kalinina
Department of Biochemistry and Molecular Medicine, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow, Russia.
Veronika Yu
VY
Sysoeva
Department of Biochemistry and Molecular Medicine, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow, Russia.
Daniyar T
DT
Dyikanov
Department of Biochemistry and Molecular Medicine, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow, Russia.
Dmitriy V
DV
Stambolsky
Department of Biochemistry and Molecular Medicine, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow, Russia.
Vsevolod A
VA
Tkachuk
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology*; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; D002118:Calcium; D009638:Norepinephrine