title: Pathological regulation of arachidonic acid release in cystic fibrosis: the putative basic defect.
abstract: The regulation of arachidonic acid release from membrane phospholipids was investigated in lymphocytes from patients with cystic fibrosis as well as control patients. No effect of either dexamethasone or fetal calf serum was seen on arachidonic acid release from cystic fibrosis lymphocytes, in contrast to control lymphocytes. In the latter cells, arachidonic acid release was inhibited by dexamethasone, fetal calf serum, or both. There were no differences in glucocorticoid receptor in lymphocytes from the two groups with regard to Kd and number of binding sites per cell. Furthermore, dexamethasone inhibited the incorporation of thymidine into lymphocytes from either group, indicating a normal functional glucocorticoid receptor. The defective regulation of arachidonic acid, resulting in an increased turnover, can explain many of the findings in cystic fibrosis, and we hypothesize that it is the basic defect causing the disease. The defect occurs at a level after the glucocorticoid receptor, which is functionally normal, and involves either the glucocorticoid-dependent phospholipase-inhibitory protein lipomodulin (lipocortin) or phospholipase A2.
mesh_terms: D017302:Annexins; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000503:physiopathology; D003907:Dexamethasone / Q000494:pharmacology; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000502:physiology
chemical_list: D017302:Annexins; D001095:Arachidonic Acids; D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D008563:Membrane Lipids; D011965:Receptors, Glucocorticoid; C030958:lipomodulin; D016718:Arachidonic Acid; D003907:Dexamethasone