AJP - Endocrinology and Metabolism, Vol 255, Issue 3 E383-E387, Copyright © 1988 by American Physiological Society
Ouabain induces secretion of proatrial natriuretic factor by rat atrial cardiocytes
K. D. Bloch, N. Zamir, D. Lichtstein, C. E. Seidman and J. G. Seidman
Cardiac Unit, Massachusetts General Hospital, Boston 02114.
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.
