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12‐ O ‐Tetradecanoylphorbol 13‐Acetate and Forskolin Modify Muscarinic Receptor‐Linked Ca 2+ Mobilization in SH‐SY5Y Neuroblastoma Cells Through Different Mechanisms
Author(s) -
Åkerman Karl E. O.,
Heikkilä Jari E.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb01899.x
Subject(s) - carbachol , forskolin , muscarinic acetylcholine receptor , 12 o tetradecanoylphorbol 13 acetate , endocrinology , medicine , cytosol , chemistry , sh sy5y , receptor , protein kinase c , biology , cell culture , biochemistry , neuroblastoma , phorbol ester , signal transduction , enzyme , genetics
The phorbol ester, 12‐ O ‐tetradecanoylphorbol 13‐acetate (TPA), which causes differentiation of SH‐SY5Y neuroblastoma cells, reduces carbachol binding and carbachol‐stimulated Ca 2+ mobilization in these cells. The decrease in responsiveness to carbachol is due partially to a reduction in the amount of Ca 2+ 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 Ca 2+ influx into the cells without affecting the cytosolic free Ca 2+ concentration. The alkaloid causes an apparent restoration of the reduced Ca 2+ 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 Ca 2+ . 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 Ca 2+ metabolism.