Icosanoid production can be decreased without alterations in cellular arachidonate content or enzyme activities required for arachidonate release and icosanoid synthesis.
We have demonstrated that icosanoid production can be inhibited by altering the distribution of arachidonate within the cell, so that it is not released from phospholipids for icosanoid synthesis. This effect was observed in a prostaglandin E2-producing cell line (HSDM1C1) by deprivation of exogenous arachidonate for 24-48 h. Icosanoid production by the cells upon bradykinin stimulation was impaired despite no change in the concentration of arachidonate within the cell and no change in the activity of cyclooxygenase, phospholipases, acyltransferases, or fatty acyl-CoA hydrolase. Associated with the decline in prostaglandin E2 production was an increase in arachidonate incorporation into ethanolamine plasmalogens and a decrease in the activity of the enzyme arachidonoyl-CoA synthetase, which may play a role in compartmentation of arachidonate within the cell. Thus, we have found that a decrease in icosanoid production can be achieved without pharmacologic intervention by a short-term restriction of exogenous arachidonate which leads to redistribution of arachidonate within phospholipids and/or subcellular membranes in the cell.
D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology; D003066:Coenzyme A Ligases / Q000378:metabolism*; D015232:Dinoprostone; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D005354:Fibrosarcoma / Q000378:metabolism; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism; D051379:Mice; D010170:Palmitoyl-CoA Hydrolase / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism; D010955:Plasmalogens / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011458:Prostaglandins E / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D010955:Plasmalogens; D011458:Prostaglandins E; C020791:phosphatidal ethanolamines; D016718:Arachidonic Acid; D019787:Linoleic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D000217:Acyltransferases; D010740:Phospholipases; D010170:Palmitoyl-CoA Hydrolase; D003066:Coenzyme A Ligases; C033896:arachidonate - CoA ligase; D015232:Dinoprostone; D001920:Bradykinin