Atrial natriuretic peptide attenuates Ca2+ oscillations and modulates plasma membrane Ca2+ fluxes in rat hepatocytes.

Abstract Background & Aims: Oscillations in cytosolic free Ca 2+ concentration are a fundamental mechanism of intracellular signaling in hepatocytes. The aim of this study was to examine the effects of atrial natriuretic peptide (ANP) on cytosolic Ca 2+ oscillations in rat hepatocytes. Methods: Cyclic guanosine monophosphate (cGMP) was measured by enzyme immunoassay. Cytosolic Ca 2+ oscillations were recorded from single aequorin-injected hepatocytes. Ca 2+ efflux from hepatocyte populations was measured by using extracellular fura-2. Ca 2+ influx was estimated by Mn 2+ quench of fluorescence of fura-2 dextran injected into single hepatocytes. Results: ANP attenuated cytosolic Ca 2+ oscillations through a decrease in their frequency. In addition, ANP dramatically stimulated plasma membrane Ca 2+ efflux and modestly inhibited basal Ca 2+ influx. All of the observed effects of ANP were mimicked by the cGMP analogue 8-bromo-cGMP (8-Br-cGMP), and were prevented by inhibition of protein kinase G. In contrast, activation of cytosolic guanylyl cyclase by sodium nitroprusside had no effect on Ca 2+ efflux, Ca 2+ influx, or Ca 2+ oscillations. Conclusions: ANP decreases the frequency of Ca 2+ oscillations and modulates plasma membrane Ca 2+ fluxes in rat hepatocytes. Attenuation of oscillatory Ca 2+ signaling in hepatocytes may represent a key role for ANP in vivo. GASTROENTEROLOGY 2002;123:1291-1303