MECHANISMS OF HORMONE AND TRANSMITTER SECRETION

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Our recent work has focussed on the processes leading to fusion between granule and plasma membranes during exocytosis in cells such as chromaffin cells, beta cells in islets of Langerhans, frog neuromuscular junction, and tracheal submucosal gland cells. Synexin, a calcium-binding membrane fusion protein found in many tissues, was found to fuse membranes by a mechanism involving membrane mixing occurring prior to volume mixing. Synexin was also found to enter membranes and change the capacitance, and simultaneously to exhibit calcium channel activity. From these and other data we have formulated a hydrophobic bridge hypothesis for membrane fusion driven by synexin. The fast-freeze electron microscopy technique has been used to measure distribution of elements and their concentrations in discrete regions of cytosol. By this method we have measured transmembrane electrical potentials across organelles in cells frozen with in a millisecond. Bovine chromaffin cells have been transplanted into regions of brain involved in pain. Stimulation of these implanted cells by nicotine administration causes a reduction in pain sensed by the recipient rats and monkeys. Cytosolic pH may be important in stimulus-secretion coupling in chromaffin and beta cells, resulting in release of adrenaline and insulin, respectively. Transient acidification is followed by promote return to ambient pH suing a Na+/H+-exchange pump in the plasma membrane. Ascorbate, an important vitamin, is critically required for biosynthesis of noradrenaline in chromaffin granules within intact chromaffin cells.