12-O-TETRADECANOYLPHORBOL 13-ACETATE AND FORSKOLIN MODIFY MUSCARINIC RECEPTOR-LINKED CA-2+ MOBILIZATION IN SH-SY5Y NEUROBLASTOMA-CELLS THROUGH DIFFERENT MECHANISMS

The phorbol ester, 12‐O‐tetradecanoylphorbol 13‐acetate (TPA), which causes differentiation of SH‐SY5Y neuroblastoma cells, reduces carbachol binding and carbachol‐stimulated Ca2+ mobilization in these cells. The decrease in responsiveness to carbachol is due partially to a reduction in the amount of Ca2+ released by the cells and partially to a decrease in the sensitivity of the cells to carbachol. These effects probably can be attributed to a reduction in muscarinic receptor number and a decrease in receptor affinity, respectively. Forskolin, an alkaloid known to cause an increase in cellular cyclic AMP, enhances Ca2+ influx into the cells without affecting the cytosolic free Ca2+ concentration. The alkaloid causes an apparent restoration of the reduced Ca2+ release, caused by TPA, but does not affect the sensitivity of the cells to carbachol. Forskolin increases the decay of carbachol‐induced increase in cytosolic Ca2+. The effects of TPA appear to be linked directly to receptor function, whereas those of forskolin are due to the effect of cyclic AMP on cellular Ca2+ metabolism. Copyright © 1990, Wiley Blackwell. All rights reserved