title: Stimulation of prostaglandin synthesis in WI-38 human lung fibroblasts following inhibition of phospholipid acylation by p-hydroxymercuribenzoate.
abstract: The release of arachidonic acid and its metabolites, prostaglandin E2 and thromboxane A2, from WI-38 human lung fibroblasts was modulated by p-hydroxymercuribenzoate. Exposure to the inhibitor resulted in a dose-dependent decrease in [1-14C]arachidonic acid uptake and incorporation into phospholipids and neutral lipid pools. Activities of lung fibroblast arachidonyl-CoA synthetase and lysolecithin acyltransferase were inhibited by 100 microM p-hydroxymercuribenzoate. [14C]Arachidonic acid labelled fibroblasts exhibited an increased release of [14C]arachidonate and [14C]prostaglandin E2 of 54% and 112%, respectively, when exposed to 100 microM of inhibitor. The stimulatory effects of 8.0 microM delta 1-tetrahydrocannabinol on arachidonate release and prostaglandin E synthesis (Burstein, S., Hunter, S.A., Sedor, C. and Shulman, S. (1982) Biochem. Pharmacol. 31, 2361-2365) were modified by the inclusion of inhibiting agent, resulting in a 608% stimulation in arachidonic acid release, while prostaglandin E2 and thromboxane A2 synthesis increased 894% and 390%, respectively, over levels obtained by untreated cells. The levels of arachidonate metabolites were altered by inhibitor when compared to cells treated with cannabinoid alone. No significant inhibition by delta 1-tetrahydrocannabinol was found on arachidonic uptake in these cells. In unlabelled studies, p-hydroxymercuribenzoate resulted in a profound, dose-dependent stimulation of prostaglandin E synthesis of 1490% at 150 microM inhibitor concentration. These results provide evidence that free arachidonate is reincorporated via acylation, thereby implicating this pathway as a possible control mechanism for the synthesis of arachidonic acid metabolites.
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000037:antagonists & inhibitors; D000215:Acylation; D002460:Cell Line; D002729:Chloromercuribenzoates / Q000494:pharmacology; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors; D003470:Culture Media / Q000032:analysis; D015232:Dinoprostone; D013759:Dronabinol / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006902:Hydroxymercuribenzoates / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis*; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*; D020245:p-Chloromercuribenzoic Acid
chemical_list: D002729:Chloromercuribenzoates; D003470:Culture Media; D006902:Hydroxymercuribenzoates; D010743:Phospholipids; D011458:Prostaglandins E; D013931:Thromboxanes; C030601:4-hydroxymercuribenzoate; D013928:Thromboxane A2; D020245:p-Chloromercuribenzoic Acid; D013759:Dronabinol; D008243:1-Acylglycerophosphocholine O-Acyltransferase; D003066:Coenzyme A Ligases; C033896:arachidonate - CoA ligase; D015232:Dinoprostone