The pathway of atrial natriuretic peptide release--from cell to plasma

Tannic acid and dextran have been used to arrest the exocytosis of secretory granules in the atria of the rat heart. By immunogold labeling with silver intensification of ultrathin sections, the arrested exocytosing granules are demonstrated to contain atrial natriuretic peptide (ANP). Extracellular core-like structures found in atria treated with tannic acid are also shown to contain atrial natriuretic peptide. This allows a pathway for the release of atrial natriuretic peptide to be traced from the surface of the myocyte, through the endomysium, into the sub-endothelial space and to the abluminal surface of the capillary endothelium. Uptake of atrial natriuretic peptide into the capillary endothelial cells was also detected. Endothelial transport and release of atrial natriuretic peptide appears to involve the caveolae and smooth vesicles of the non-selective endothelial transport system. No labeling was detected in the endothelial cells of the endocardium or in the mesothelial cells of the epicardium. A disruption of arrested granule cores is seen after dextran treatment. This, and the variation in the labeling of extracellular cores observed, is consistent with the possibility that the cleavage of atrial natriuretic peptide prohormone may be initiated upon the fusion of a granule with the plasma membrane, and continue during the passage of the core material through the extracellular space, with a gradual loss of the active moiety from the disrupted core.