Although exocytosis is now known to be the universal method by which proteins are released from eukaryotic cells, we know surprisingly little of the mechanism by which exocytosis occurs. One reason for this is that it has proved difficult to capture sufficient of these evanescent events to permit their study. The difficulty with which exocytoses can be visualized with standard preparative techniques varies among tissues, but the problem is particularly apparent in the mammalian nervous system. Tannic acid has recently been introduced as an agent by which exocytosed granule cores can be captured and visualized electron-microscopically. Application of tannic acid to the magnocellular neurosecretory system reveals exocytoses from all parts of their terminal arborization within the neural lobe, and also from their dendrites within the hypothalamus. Quantification of the exocytoses in unstimulated tissue and in tissue stimulated by a variety of exogenous and endogenous mechanisms indicates: (a) that exocytosis occurs equally from each unit of membrane of the perivascular nerve endings, and of the axonal swellings that were previously thought to be sites of granule storage, rather than release; (b) that, in the nerve endings, a greater proportion of the stored granules are exocytosed, and thus the endings are specialized for release not by any particular property of their membrane, but by a high surface membrane:volume ratio. Together, the data cast doubt on the hypothesis that exocytosis occurs only at some functionally specialized sites at certain loci in the membrane. Rather, the data favour the hypothesis that magnocellular granules can fuse with any part of the membrane, depending on constraints imposed by the cytoskeleton, and a local increase in cytosolic free calcium level. When applied to hypothalamic central nervous tissue, tannic acid reveals that exocytosis of dense-cored synaptic vesicles occurs preferentially, but not exclusively, at the membrane apposed to the postsynaptic element. However, about half of all exocytoses from synaptic boutons occur at bouton membrane unrelated to the synaptic cleft. In all tissues studied, tannic acid reveals a heterogeneity among secretory cells in the extent of exocytosis that occurs in response to stimulation, and permits an analysis of the degree to which secretion is polarized in any one direction. These results question long-held assumptions concerning the site at which neurones release transmitters and modulators. Tannic acid seems likely to prove a potent tool in the investigation of both the mechanism of exocytosis and the ways in which different types of cells adapt the process to perform their physiol

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