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


METHODS
Cyclic guanosine monophosphate (cGMP) was measured by enzyme immunoassay. Cytosolic Ca2+ oscillations were recorded from single aequorin-injected hepatocytes. Ca2+ efflux from hepatocyte populations was measured by using extracellular fura-2. Ca2+ influx was estimated by Mn2+ quench of fluorescence of fura-2 dextran injected into single hepatocytes.


RESULTS
ANP attenuated cytosolic Ca2+ oscillations through a decrease in their frequency. In addition, ANP dramatically stimulated plasma membrane Ca2+ efflux and modestly inhibited basal Ca2+ 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 Ca2+ efflux, Ca2+ influx, or Ca2+ oscillations.


CONCLUSIONS
ANP decreases the frequency of Ca2+ oscillations and modulates plasma membrane Ca2+ fluxes in rat hepatocytes. Attenuation of oscillatory Ca2+ signaling in hepatocytes may represent a key role for ANP in vivo.
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D002118:Calcium