Arachidonic acid regulates the phosphoinositide signal transduction pathway in submandibular acinar cells.
Modulation of the phosphoinositide signal transduction pathway by arachidonic acid (AA) in collagenase-dispersed rat submandibular acinar cells was investigated. The muscarinic agonist, carbachol, stimulated PIP2 hydrolysis and the generation of IP3 to five-fold the control levels. This response was inhibited by 75% on pre-treatment of cells with AA. The AA inhibitory effect was not duplicated by a range of prostaglandins and leukotrienes and was not reversed by blockers of the cyclo-oxygenase and lipoxygenase synthetic pathways, indicating that AA action was not mediated by eicosanoid metabolites. Additional experiments confirmed that the enzyme, protein kinase C, was also not a mediator of the AA effect. Arachidonic acid did not affect the uptake of radioactive inositol into acinar cells, but it did inhibit the incorporation of inositol into inositol phospholipids of the phosphoinositide cycle. In studies on inositol phospholipid turnover, AA alone reduced the level of PIP2 but not of PIP or PI. Under conditions of PI cycle stimulation with carbachol, AA significantly lowered PIP2 and PIP but not PI. These findings suggest that arachidonic acid may regulate the phosphoinositide response by inhibiting the synthetic phase of the cycle at a locus distal to PI generation.
Chung
H C
HC
Department of Oral Biology, Faculty of Dentistry, University of Manitoba, Winnipeg.
Fleming
N
N
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D006868:Hydrolysis; D007294:Inositol / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D007295:Inositol Phosphates / Q000037:antagonists & inhibitors / Q000378:metabolism; D015289:Leukotrienes / Q000494:pharmacology; D008297:Male; D009077:Mucins / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011453:Prostaglandins / Q000494:pharmacology; D011493:Protein Kinase C / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects*; D013363:Submandibular Gland / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*
D007295:Inositol Phosphates; D015289:Leukotrienes; D009077:Mucins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D011453:Prostaglandins; D016718:Arachidonic Acid; C044259:inositol 1,4-bis(phosphate); D007294:Inositol; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D011493:Protein Kinase C