Coordination of calcium signalling by endothelial-derived nitric oxide in the intact liver

Calcium ions (Ca2+) and nitric oxide (NO) are key signalling molecules that are implicated in the regulation of numerous cellular processes. Here we s how that, in the intact liver, stimulation of endothelial cells by bradykin in coordinates the propagation of vasopressin-dependent intercellular Ca2waves across hepatic plates, and markedly increases the frequency of Ca2+ o scillations in individual hepatocytes. Modulation of Ca2+ oscillations by b radykinin is lost following isolation of hepatocytes, but restored in co-cu ltures of hepatocytes and endothelial cells. The sensitizing effects of bra dykinin are mimicked by NO donors and abrogated by NO inhibitors. Thus, cro sstalk between NO and Ca2+ signalling pathways through the microvasculature is probably an important mechanism for the coordination of liver function and may have a function in other organs.