ANP stimulates hepatocyte Ca2+ efflux via plasma membrane recruitment of PKGIalpha.
In rat hepatocytes, atrial natriuretic peptide (ANP) elevates cGMP through activation of particulate guanylyl cyclase and attenuates Ca(2+) signals by stimulating net plasma membrane Ca(2+) efflux. We show here that ANP-stimulated hepatocyte Ca(2+) efflux is mediated by protein kinase G (PKG) isotype I. Furthermore, we show that ANP recruits endogenous PKGIalpha, but not PKGIbeta, to the plasma membrane. These effects are mimicked by 8-bromo-cGMP, but not by the soluble guanylyl cyclase activators, sodium nitroprusside and YC-1. We propose that ANP, through localized cGMP elevation, promotes plasma membrane recruitment of PKGIalpha, which, in turn, stimulates Ca(2+) efflux.
Stratton
Rebecca C
RC
Department of Biological Sciences, The University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
Squires
Paul E
PE
Green
Anne K
AK
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013873:Thionucleotides / Q000494:pharmacology
D007191:Indazoles; D013873:Thionucleotides; C472610:atrial natriuretic peptide, rat; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D009599:Nitroprusside; D009320:Atrial Natriuretic Factor; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D002118:Calcium