Effect of inhibitors of eicosanoid metabolism on release of [3H]noradrenaline from the human neuroblastoma, SH-SY5Y.
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 [3H]-noradrenaline ([3H]NA) from the human neuroblastoma clone SH-SY5Y with IC50 values of 10, 15, and 30 microM, 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 microM). Under these conditions there was a selective increase in content of membrane polyunsaturated fatty acids of the omega 6 series, including arachidonic acid; however, these changes did not effect potassium-, veratridine-, carbachol-, or calcium ionophore-evoked release of [3H]NA.
Vaughan
P F
PF
Department of Cardiovascular Studies, University of Leeds, England.
Murphy
M G
MG
Ball
S G
SG
D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003512:Cyclohexanones / Q000494:pharmacology; D015777:Eicosanoids / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D006801:Humans; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008049:Lipase / Q000037:antagonists & inhibitors; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D009930:Organic Chemicals; D011188:Potassium / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D003512:Cyclohexanones; D015777:Eicosanoids; D008041:Linoleic Acids; D016859:Lipoxygenase Inhibitors; D009930:Organic Chemicals; C080291:LY 270766; D016718:Arachidonic Acid; D000001:Calcimycin; D009637:Masoprocol; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D002217:Carbachol; D019787:Linoleic Acid; D008049:Lipase; D011188:Potassium; D009638:Norepinephrine