Cells of the adrenal medulla share the embryological origin of neuronal cells. They are anatomically and biochemically very similar to sympathetic neurons. They can be prepared in large quantities and in a homogeneous state, making possible experiments on structure and secretion that would be very difficult to do with nerve cells. We have been studying the secretion of catecholamines from cultured adrenal cells on 50 mm plastic beads which we can put into a small chamber. We pass a stream of buffer over the cells and upon injection of stimulant, can monitor the release of catecholamine on-line. This technique has led to several very interesting discoveries, including the fact that nucleotides released along with the catecholamines act as feedback modulators of release, apparently binding to purinergic receptors on the cells.

Edward W. Westhead Cells of the Adrenal Medulla as a Neuronal Model The purinergic responses are complex, however. Not only can ATP, ADP and adenosine inhibit secretion, but under some conditions, they can produce dramatic increases in secretion. We combine biochemical analyses, electrophysiology (patch-clamp technique) and video-imaging microscopy to explore these phenomena. Biochemical techniques allow us to relate changes in second-messenger concentration to the modulation of secretion, and to identify the participation of specific GTP-binding proteins ("G-proteins") in the signalling pathway.

With the patch-clamp technique we can measure the effect of modulatory stimulants on the influx of specific ions (especially Ca2+) into the cell and we can introduce directly into the cell agents that modify specific known pathways to test for their participation in the response. Videoimaging micro-scopy allows us to observe changes in internal Ca2+ concentration and changes in membrane potential in individual cells of a population. This has allowed us, for example, to find out that the cell population is quite heterogeneous in response to some stimulants. ATP, for example, causes a powerful influx of Ca2+ into a distinct population of cells, while other cells are non-responsive.

Representative Publications:

Chern, Yi-J., Bott, M., Chu, P.J., Lin, Y.J., Kao, L.S., and Westhead, E.W. (1992).

The adenosine analogue N6-L-Phenylisopropyladenosine inhibits catecholamine secretion from bovine adrenal medulla cells by inhibiting calcium influx. J. Neurochem. 59: 1399-1404.

Lin, L.F., Kim, K.T., and Westhead, E.W. (1993).

Protein phosphorylation at a postreceptor site can block desensitization and induce potentiation of secretion in chromaffin cells. J. Neurochem. 60: 1491-1497.

Lin, L.F., Kao, L.-S., and Westhead, E.W. (1994).

Agents that promote protein phosphorylation inhibit the activity of the Na+/Ca2 exchanger and prolong Ca2+ transients in bovine chromaffin cells. J. Neurochem. 63: 1941-1947.

Xiong, Y., Westhead, E.W., and Slakey, L.L. (1995).

Role of phosphodiesterase isoenzymes in regulating intracellular cyclic AMP in adenosine-stimulated smooth muscle cells. Biochem. J. 305: 627-633.

Reichsman, F., Santos, S., and Westhead, E.W. (1995).

Two distinct ATP receptors activate calcium entry and internal calcium release in bovine chromaffin cells. J. Neurochem. 65: 2080-2086.

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