Functional expression of adrenoreceptors in mesenchymal stromal cells derived from the human adipose tissueстатья

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[1] Functional expression of adrenoreceptors in mesenchymal stromal cells derived from the human adipose tissue / P. Kotova, V. Sysoeva, O. Rogachevskaja et al. // Biochimica et Biophysica Acta - General Subjects. — 2014. 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 Ca2+ imaging. As a whole, a MSC population exhibited functional heterogeneity. Although a variety of first messengers was capable of stimulating Ca2+ 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 α1Β-, α2Α-, and β2- adrenoreceptors in MSCs. Their sensitivity to subtype-specific adrenergic agonists/antagonists and certain inhibitors of Ca2+ signaling indicated that largely the α2Α- isoform coupled to PLC endowed MSCs with sensitivity to noradrenaline. The all-or-nothing dose-dependence was characteristic of responsivity of robust adrenergic MSCs. Noradrenalin never elicited small or intermediate responses but initiated large and quite similar Ca2+ transients at all concentrations above the threshold. The inhibitory analysis and Ca2+ uncaging implicated Ca2+-induced Ca2+ release (CICR) in shaping Ca2+ signals elicited by noradrenalin. 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: noradrenalin initially triggers a local and relatively small Ca2+ signal, which next stimulates CICR, thereby being converted into a global Ca2+ signal. [ DOI ]

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