Angiotensin II activates different calcium signaling pathways in adipocytes

• Angiotensin II type 1 and 2 receptors are expressed in adipocytes and induces sCa2+i increases and oscillations.
• Activation of the two receptor types by one agonist (Angiotensin II) paves the way to the convergence of signalling pathways, regulating the amplitude and character of Ca2+ response.
• AngII-induced Ca2+- responses are sensitive to inhibition of phospholipase C (PLC) or inositol 1,4,5-trisphosphate receptors (IP3R).
• AngII-induced Ca2+- responses are sensitive to inhibition of PI3Kγ, Akt/PKB and ryanodine receptors (RyR).

Angiotensin II (Ang II) is an important mammalian neurohormone involved in reninangiotensin system. Ang II is produced both constitutively and locally by RAS systems, including white fat adipocytes. The influence of Ang II on adipocytes is complex, affecting different systems of signal transduction from early Са2+ responses to cell proliferation and differentiation, triglyceride accumulation, expression of adipokine-encoding genes and adipokine secretion. It is known that white fat adipocytes express all RAS components and Ang II receptors (АТ1 and АТ2). The current work was carried out with the primary white adipocytes culture, and Са2+ signaling pathways activated by Ang II were investigated using fluorescent microscopy. Са2+-oscillations and transient responses of differentiated adipocytes to Ang II were registered in cells with both small and multiple lipid inclusions. Using inhibitory analysis and selective antagonists, we now show that Ang II initiates periodic Са2+-oscillations and transient responses by activating АТ1 and АТ2 receptors and involving branched signaling cascades:1) Ang II → Gq → PLC → IP3 → IP3Rs → Ca2+2) Gβγ → PI3Kγ → PKB3) PKB → eNOS → NO → PKG4) CD38 → cADPR → RyRs → Ca2+In these cascades, AT1 receptors play the leading role. The results of the present work open a perspective of using Ang II for correction of signal resistance of adipocytes often observed during obesity and type 2diabetes.

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