Regulation of Prostaglandin Biosynthesis in Cultured Renal Medullary Interstitial Cells
Advances in the understanding of arachidonic acid metabolism have led to the isolation and identification of the prostaglandins (PGs), thromboxanes, prostacyclin, and leukotrienes. It is now known that virtually every cell of mammalian organisms is capable of initiating the metabolism of arachidonic acid, which was originally thought to be a unique product of the seminal vesicle. In every cell type the initiation of the synthetic cascade involves the release of arachidonic acid from its cellular storage pool, predominantly phospholipids and triglycerides, and conversion to the prostaglandin endoperoxides PGG2 and PGH2 by the cyclooxygenase enzyme. The subsequent synthesis of prostaglandins E2 and F2α, thromboxane A2, or prostacyclin (PGI2) is dependent upon the presence or absence of the specific enzymes responsible for the conversion of PGG2 and PGH2 to the respective end products. Thus an understanding of the regulation of prostaglandin biosynthesis at the cellular level is dependent upon the study of the rate-limiting step in the biosynthetic cascade. This rate-limiting reaction is the release of arachidonic acid from the cellular storage pool. Once liberated from the complex lipids within the cellular matrix and cell wall, the free arachidonate enters the cytoplasm and is rapidly metabolized. An understanding of the factors which affect the rate of arachidonic acid release from the phospholipid—triglyceride storage pool must therefore be the focus of an analysis of the cellular regulation of prostaglandin biosynthesis.
KeywordsArachidonic Acid Angiotensin Converting Enzyme Inhibitor Phospholipase Activity Arachidonic Acid Release PGE2 Synthesis
Unable to display preview. Download preview PDF.
- 2.Muirhead EE, Germain G, Leach BE, et al: Production of renomedullary prostaglandins by renomedullary interstitial cells in tissue culture. Circ Res 30–31 (Suppl II): 161–170, 1972.Google Scholar
- 5.Zusman RM, Brown CA: Role of phospholipase in the regulation of prostaglandin E2 biosynthesis by rabbit renomedullary interstitial cells in tissue: Effects of angiotensin II, potassium, hyperosmolality, dexamethasone and protein synthesis inhibition. Adv Prost Thromb Res 6: 243–248, 1980.Google Scholar
- 8.Beck TR, Hassid, Dunn MJ: The effect of arginine vasopressin and its analogues on the synthesis of PGE2 by rat renal medullary interstitial cells in culture. Pharmacol Exp Ther 215: 15–19, 1980.Google Scholar
- 9.Dunn MJ, Kinter LB, Beeuwkes R, et al: Interaction of vasopressin and renal prostaglandins in the homozygous diabetes insipidus rat. Adv Prost Thromb Res 7: 1009–1016, 1980.Google Scholar
- 16.Hirata F, Axelrod J: Biochemical mechanism of signal transduction across biomembranes. Submitted for publication.Google Scholar
- 19.Cushman DW, Cheung HS, Sabo EF, et al: Angiotensin converting enzyme inhibitors: Evolution of a new class of antihypertensive drugs, in Horowitz ZP (ed): Angiotensin Converting Enzyme Inhibitors: Mechanisms of Action and Clinical Implications, Baltimore, Urban and Schwarzenberg, 1981, pp 3–26.Google Scholar
- 25.Vinci JM, Horwitz D, Zusman RM, et al: The effect of converting enzyme inhibition with SQ 20881 on plasma and urinary kinins, prostaglandin E, and angiotensin II in hypertensive man. Hypertension 1: 416–426, 1979.Google Scholar
- 29.Galler M, Folkert VW, Schlondorff D. Effect of converting enzyme inhibitor of prostaglandin synthesis by isolated rat glomeruli. Clin Res 29: 271A, 1981.Google Scholar