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Chromaffin cells of the mouse adrenal medulla were found by transmission electron microscopy (TEM) to exhibit ultrastructural changes suggestive of piecemeal degranulation (PMD), a unique model of cell secretion characterized by the slow release of granule materials without granules opening to the cell exterior. The expression of PMD was recognized in both adrenalineand noradrenaline-containing cells. Ultrastructural changes included specific granule and cytoplasmic morphologies. In adrenaline-releasing cells the granule content was loosely packed or condensed, and surrounded by a clear halo. In noradrenaline-storing cells, the granule material appeared asymmetically arranged and exhibited characteristic "semilunar" electron-dense domains within the granule chambers. Notably, altered granules did not fuse with each other or with the plasma membrane, and were intermingled with normal, resting granules. Large, empty cytoplasmic containers or vacuoles filled with partially dissolved matrices were frequently observed. In addition, both adrenaline-and noradrenaline-storing cells presented a rich supply of membrane-bound, smooth vesicles (50 -200 nm diameter) that were either free in the cytoplasm or attached to granules. The finding of ultrastructural features characteristic of PMD in adrenal chromaffin cells suggests that such a secretory model may be an alternative secretory pathway to regulated exocytosis. Moreover, these results support the hypothesis that PMD may be a general degranulation pattern in cells involved in paracrine-endocrine secretion. Anat Rec Part A 270A: 103-108, 2003.

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