title: Ouabain induces secretion of proatrial natriuretic factor by rat atrial cardiocytes.
abstract: Neonatal rat atrial and ventricular cardiocytes in primary culture secrete proatrial natriuretic factor (proANF), the 126-amino acid precursor of atrial natriuretic factor (ANF). The cellular mechanisms of proANF secretion differ in the two cell types: atrial cardiocytes store proANF in abundant secretory granules before secretion, whereas ventricular cardiocytes secrete the precursor rapidly after synthesis. In this study, we used the Na+-K+-adenosinetriphosphatase (ATPase) inhibitor ouabain to investigate the functional significance of these differing secretory mechanisms. Ouabain increased immunoreactive ANF (iANF) secretion by atrial cardiocytes 1.5- to 2.4-fold. Metabolic labeling studies demonstrated that proANF was the form of iANF released in response to ouabain. Ventricular secretion of iANF was unaffected by the Na+-K+-ATPase inhibitor. These observations are consistent with a model in which atrial cardiocytes are able to release proANF via a regulated secretory pathway, whereas ventricular cardiocytes utilize a constitutive secretory pathway. The ability of ouabain to stimulate proANF secretion suggests that an increase in intracellular calcium concentration may promote fusion of secretory granules with atrial cell membranes thereby mediating exocytosis of stored proANF.
authors.affiliation: Cardiac Unit, Massachusetts General Hospital, Boston 02114.
authors.forename: K D
authors.initials: KD
authors.lastname: Bloch
authors.forename: N
authors.initials: N
authors.lastname: Zamir
authors.forename: D
authors.initials: D
authors.lastname: Lichtstein
authors.forename: C E
authors.initials: CE
authors.lastname: Seidman
authors.forename: J G
authors.initials: JG
authors.lastname: Seidman
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology*; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats
chemical_list: D011498:Protein Precursors; D000001:Calcimycin; D010042:Ouabain; D009320:Atrial Natriuretic Factor