title: Inhibition effect of arachidonic acid on hypoxia-induced [Ca(2+)](i) elevation in PC12 cells and human pulmonary artery smooth muscle cells.
abstract: [Ca(2+)](i) elevation is a key event when O(2) sensitive cells, e.g. PC12 cells and pulmonary artery smooth muscle cells, face hypoxia. Ca(2+) entry pathways in mediating hypoxia-induced [Ca(2+)](i) elevation include: voltage-gated Ca(2+) channels (VGCCs), transient receptor potential (TRP) channel and Na(+)-Ca(2+) ex-changer (NCX). In the pulmonary artery, accumulated evidence strongly suggests that prostaglandins (PGs) are involved in pulmonary inflammation and cause vasoconstriction during hypoxia. In this study, we investigated the effect of arachidonic acid (AA), the upstream substrate for PGs, on hypoxia response in O(2) sensitive cells. Exogenous application of AA significantly inhibited hypoxia-induced [Ca(2+)](i) elevation. This effect was due to AA itself rather than its degenerative products. The pharmacological modulation of endogenous AA showed that the prevention of AA generation by blockage of cPLA2, diacylglycerol (DAG) lipase and fatty acid hydrolysis (FAAH), augments hypoxia-induced [Ca(2+)](i) elevation, whereas prevention of AA degeneration attenuates hypoxia-induced [Ca(2+)](i) elevation. Over-expression of COX2 enhances hypoxia-induced [Ca(2+)](i) elevation and this enhancement is reversed by exogenous AA. Our results suggest that AA inhibits hypoxia response. The dynamic alterations in cellular lipids might determine cell response to hypoxia.
authors.affiliation: Department of Physiology, The Medical School, University of Birmingham, Vincent Drive, Birmingham, UK.
authors.forename: Fei
authors.initials: F
authors.lastname: Meng
authors.forename: Wilson King Lim
authors.initials: WK
authors.lastname: To
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D016716:PC12 Cells / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology*; D051381:Rats
chemical_list: D004791:Enzyme Inhibitors; D016718:Arachidonic Acid; D011189:Potassium Chloride; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D002118:Calcium