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Effect of Inhibitors of Eicosanoid Metabolism on Release of [ 3 H]Noradrenaline from the Human Neuroblastoma, SH‐SY5Y
Author(s) -
Vaughan Peter F. T.,
Murphy Mary G.,
Ball Stephen G.
Publication year - 1993
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.1471-4159.1993.tb03297.x
Subject(s) - nordihydroguaiaretic acid , arachidonic acid , lipoxygenase , chemistry , calcium , sh sy5y , veratridine , biochemistry , potassium , nigericin , carbachol , endocrinology , medicine , cell culture , biology , sodium , enzyme , neuroblastoma , receptor , organic chemistry , sodium channel , membrane , genetics
Nordihydroguaiaretic acid (NDGA; a lipoxygenase inhibitor), LY‐270766 (an inhibitor of 5‐lipoxygenase), and the diacylglycerol lipase inhibitor RG 80267 completely eliminated potassium‐evoked release of [ 3 H]noradrenaline ([ 3 H]NA) from the human neuroblastoma clone SH‐SY5Y with IC 50 values of 10, 15, and 30 μ M , respectively. In contrast, these inhibitors only partially inhibited carbachol‐evoked release and had little effect on the calcium ionophore A23187‐evoked release of NA in this cell line. Arachidonic acid partially inhibited potassium‐ and A23187‐evoked release but did not reverse the inhibition of potassium‐evoked release observed in the presence of RG 80267. These studies suggest that arachidonic acid (or its lipoxygenase products) are not important intermediates in the regulation of exocytosis in SH‐SY5Y. This conclusion is strengthened by our studies in which SH‐SY5Y cells were grown in medium supplemented with bovine serum albumin‐linoleic acid (50 μ M ). Under these conditions there was a selective increase in content of membrane polyunsaturated fatty acids of the ω6 series, including arachidonic acid; however, these changes did not effect potassium‐, veratridine‐, carbachol‐, or calcium ionophoreevoked release of [ 3 H]NA.