Abstract
Prostaglandins (PGs) are products of polyunsaturated acid metabolism, particularly arachidonic acid (AA) released from membrane phospholipids by the action of phospholipase A2 in response to a variety of physical, chemical, and neurohormonal factors. AA is rapidly metabolized to oxygenated products by two distinct enzymatic pathways: cyclooxygenase and lipoxygenase. The intermediate cyclooxygenase products are converted to primary PGs, while the lipoxygenase products are converted to leukotrienes. The generation of various cyclooxygenase products varies from tissue to tissue. Aspirin and related antiinflammatory drugs reduce tissue biosynthesis of all cyclooxygenase products; their therapeutic effects and side effects parallel the inhibition of cyclooxygenase. Exogenous PGs exhibit a broad spectrum of effects. PGs of the E series and PGI2 are generated by the endothelium and the vessel wall to maintain the microcirculation and to counteract the vasoconstrictive and proaggregatory actions of thromboxane A2 (TXA2). Exogenous PGs of the E and I series are potent vasodilators in various vascular beds, and result in decreased systemic blood pressure and reflex stimulation of heart rate. PGEs and PGI2 increase renal blood flow and provoke diuresis and natriuresis, partly by modulating the renin-angiotensin-aldosterone system. PGFs contract the bronchial and gut muscle, while PGEs and PGI2 have opposite effects. PGEs and PGFs, but not PGI2, cause a strong contraction of the uterine muscle, hence their undesirable uterotonic effects. PGEs relax bronchial muscle, whereas PGFs cause bronchoconstriction; their imbalance may contribute to the high bronchial tone in bronchial asthma. PGs of the E and I series and TXA2 are generated by the gastrointestinal mucosa and released into the lumen upon neural or hormonal stimulation; they probably participate in the maintenance of mucosal integrity and microcirculation. Exogenous PGs of the E and I series inhibit gastric acid secretion and stimulate alkaline secretion while increasing mucosal blood flow. All PGs, including those noninhibitory for acid secretion, are cytoprotective against various ulcerogens and necrotizing agents. The classic PGs constitute only a small fraction of biologically active products of AA metabolism, and recent studies on the lipoxygenase products emphasize their biological activity and involvement in a variety of pathological conditions.
Similar content being viewed by others
References
Kurzok R, Lieb C: Biochemical studies of human semen: II The action of semen on the human uterus. Proc Soc Exp Biol Med 28:268–272, 1930
von Euler US: A depressor substance in the vesicular gland. J Physiol 88:213–234, 1935
Goldblatt MW: Properties of human seminal plasma. J Physiol 84:208–218, 1935
Bergstrom S, Sjovall J: The isolation of prostaglandin E from sheep prostate glands. Acta Chem Scand 14:1701–1705, 1960
Hamberg M, Svensson J, Wakabayashi T, Samuelsson B: Isolation and structure of two prostaglandin endoperoxides that cause platelet aggregation. Proc Natl Acad Sci USA 71:345–349, 1974
Nugteren DH, Hazelhof E: Isolation and properties of intermediates in prostaglandin biosynthesis. Biochim Biophys Acta 326:448–461, 1973
Hamberg M, Svensson J, Samuelsson B: Thromboxanes. A new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci USA 72:2994–2998, 1975
Bunting S, Gryglewski R, Moncada S, Vane JR: Arterial walls generate from prostaglandin endoperoxides a substance (prostaglandin X) which relaxes strips of mesenteric and coeliac arteries and inhibits platelet aggregation. Prostaglandins 12:897–913, 1976
Bray MA: The pharmacology and pathophysiology of leukotriene B4. Br Med Bull 39:249–254, 1983
Borgeat P, Samuelsson B: Metabolism of arachidonic acid in polymorphonuclear leukocytes. Structural analysis of novel hydroxylated compounds. J Biol Chem 254:7865–7869, 1979
Caton MPL: Chemistry structure and availability.In The Prostaglandins. MF Cuthbert (ed). London, William Heinemann Medical Books, 1973, pp 1–22
Dyeberg J, Bang HO, Stoffersen E, Moncada S, Vane RJ: Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet 2:117–119, 1978
Granstrom E: Biosynthesis of prostaglandins and thromboxanes.In The Prostaglandin System. F. Berti, GP Velo (eds). New York, Plenum Press, 1981, pp 15–25
Bakhle YS: Synthesis and catabolism of cyclooxygenase products. Br Med Bull 39:214–218, 1983
Taylor GW, Morris HR: Lipoxygenase pathways. Br Med Bull 39:219–222, 1983
Piper PJ, Vane JR: The release of prostaglandins from lung and other tissues. Ann NY Acad Sci 180:363–385, 1971
McGiff JC, Crowshaw K, Terragno NA, Malik KU, Lonigro AJ: Differential effect of noradrenaline and renal nerve stimulation on vascular resistance in the dog kidney and the release of a prostaglandin E-like substance. Clin Sci 42:223–233, 1972
McGiff JC, Malik KU, Terragno NA: Prostaglandins as determinants of vascular reactivity. Fed Proc 35:2382–2387, 1976
Brandt RA, Dembinska-Kiec A, Korbut R, Gryglewski RJ, Nowak J: Release of prostacyclin from the human pulmonary vascular bed in response to cholinergic stimulation. Naunyn Schmiedebergs Arch Pharmacol 325:69–75, 1984
Gimbrone MA, Alexander BW: Angiotensin II stimulation of prostaglandin production in cultured human vascular endothelium. Science 189:219–220, 1975
Ramwell PW, Shaw JE, Douglas WW, Poisner AA: Efflux of prostaglandin from adrenal glands stimulated with acetylcholine. Nature 210:273–274, 1966
Granstrom E, Diczfalusy U, Hamberg M, Hansson G, Malmsten C, Samuelsson B: Thromboxane A2: Biosynthesis and effects on platelets.In Prostaglandins and the Cardiovascular System. JA Oates (ed). New York, Raven Press, 1982, pp 15–58
Williams TJ: Interactions between prostaglandins, leukotrienes and other mediators of inflammation. Br Med Bull 39:239–242, 1983
Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature 231:232–235, 1971
Ferreira SH: A discussion on the mode of action of nonsteroid antiinflammatory drugs: Inhibition of prostaglandin synthesis.In The Prostaglandin System. F. Berti, GP Velo (eds). New York, Plenum Press, 1981, pp 139–168
Mehta J, Mehta P, Ostrowski N: Stimulation of vessel wall prostacyclin by selective thromboxane synthetase inhibitor OKY 1581. Prostaglandins, Leukotrienes, Med 12:49–52, 1983
Bunting S, Simmons PM, Moncada S: Inhibition of platelet activation by prostacyclin: Possible consequences in coagulation and anticoagulation. Thromb Res 21:89–102, 1981
Moncada S, Herman AG, Higgs EA, Vane JK: Differential formation of prostacyclin (PGX or PGI2) by layers of the arterial wall. An explanation for the antithrombotic properties of vascular endothelium. Thromb Res 11:323–324, 1977
MacIntyre DE, Pearson JD, Gordon JL: Localisation and stimulation of prostacyclin production in vascular cells. Nature 271:549–551, 1978
Moncada S, Korbut R, Bunting S, Vane JR: Prostacyclin is a circulating hormone. Nature 273:767–768, 1978
Dusting GJ, Moncada S, Vane JR: Prostacyclin: Its biosynthesis, actions, and clinical potential.In Prostaglandins and the Cardiovascular System. JA Oates (ed). New York, Raven Press, 1982, pp 59–106
Moncada S, Vane JR: Unstable metabolites of arachidonic acid and their role in haemostasis and thrombosis. Br Med Bull 34:129–135, 1978
Higgs EA, Higgs GA, Moncada S, Vane JR: Prostacyclin (PGI2) inhibits the formation of platelet thrombi in arterioles and venules of the hamster cheek pouch. Br J Pharmacol 63:535–539, 1978
Konturek SJ, Robert A: Cytoprotection of canine gastric mucosa by prostacyclin: Possible mediation by increased mucosal blood flow. Digestion 25:155–163, 1982
Kadowitz PJ, Lippton HL, McNamara DB, Spannhake EW, Hyman AL: Action and metabolism of prostaglandins in the pulmonary circulation.In Prostaglandins and the Cardiovascular System. JA Oates (ed). New York, Raven Press, 1982, pp 333–356
Dusting GJ, Chapple DJ, Hugles R, Moncada S, Vane JR: Prostacyclin induces coronary vasodilation in anaesthetized dogs. Cardiovasc Res 12:720–730, 1978
Gerber JG, Nies AS, Friesinger GC, Gerkens JF, Branch RA, Oates JA: The effects of PGI2 on canine renal function and hemodynamics. Prostaglandins 16:519–528, 1978
Wennmalm A: Participation of prostaglandins in the regulation of peripheral vascular resistance.In Prostaglandins and the Cardiovascular System. JA Oates (ed). New York, Raven Press, 1982, pp 303–331
Harrison HE, Reece AH, Johnsson M: Decreased vascular prostacyclin in experimental diabetes. Life Sci 23:351–356, 1978
Hirsh PD, Hillis LD, Campbell WD, Firth BG, Willerson JT: Release of prostaglandins and thromboxane into the coronary circulation in patients with ischemic heart disease. N Engl J Med 304:685–691, 1981
Carlson LA, Ekelund LG, Oro L: Clinical, metabolic and cardiovascular effects of different prostaglandins in man. Acta Med Scand 188:553–559, 1970
Larrson C, Anggard E: Regional differences in the formation and metabolism of prostaglandins in the rabbit kidney. Eur J Pharmacol 21:30–36, 1976
Whorton AR, Smigel M, Oates JA, Frolich JC: Regional differences in prostaglandin formation by the kidney. Biochim Biophys Acta 529:176–180, 1978
Terragno NA, Terragno DA, McGiff JC: Contribution of prostaglandins to the renal circulation in conscious, anesthetized, and laparotomized dogs. Circ Res 40:590–595, 1977
Hassid A, Dunn MJ: Microsomal prostaglandin biosynthesis of human kidneys. J Biol Chem 255:2472–2475, 1980
Chang LCT, Splawinski JA, Oates JA, Nies AS: Enhanced renal prostaglandin production in the dog. II Effects on intrarenal hemodynamics. Circ Res 36:204–207, 1975
Gerber JG, Anderson RJ, Schrier RW, Nies AS: Prostaglandins and the regulation of renal circulation and function.In Prostaglandins and the Cardiovascular System. JA Oates (ed). New York, Raven Press, 1982, pp. 227–254
Gross JB, Bartter FC: Effects of prostaglandins E1, A1 and F2 on renal handling of salt and water. Am J Physiol 225:218–224, 1973
Romero JC, Dunlap CL, Strong CG: The effect of indomethacin and other antiinflammatory drugs on the reninangiotensin system. J Clin Invest 58:282–288, 1976
Frolich JC, Hollifield JW, Dormois JC, Frolich BL, Seyberth H, Michelakis AM, Oates JA: Suppression of plasma renin activity by indomethacin in man. Circ Res 39:447–452, 1976
Fisher JW, Gross DM: Effects of prostaglandins on erythropoesis.In Prostaglandins in Haematology. M Silver, BJ Smith, JJ Kocsis (eds). New York, Spectrum Publications, 1977, pp 159–185
Cuthbert MF: Prostaglandins and respiratory smooth muscle.In The Prostaglandins. MF Cuthbert (ed). London, William Heinemann Medical Books, 1973, pp 253–285
Thor P, Konturek JW, Konturek SJ, Anderson JH: Role of prostaglandins in control of intestinal motility. Am J Physiol 248:G353-G359, 1985
Bennett A, Murray JG, Wyllie JH: Occurrence of prostaglandin E2 in the human stomach, and a study of its effects on human isolated gastric muscle. Br J Pharmacol 32:339–349, 1968
Bennett A, Stockley HL: The contribution of prostaglandins in the muscle of human isolated small intestine to neurogenic responses. Br J Pharmacol 61:573–578, 1977
Bennett A, Eley KG, Stockley HL: The effects of prostaglandins on guinea pig isolated intestine and their possible contribution to muscle activity and tone. Br J Pharmacol 54:197–204, 1975
Behrman HR, Anderson GG: Prostaglandins in reproduction. Arch Intern Med 133:77–78, 1974
Anderson GG, Facog M, Steege JF: Clinical experience using intraamniotic prostaglandin F2 for midtrimester abortion in 600 patients. Obstet Gynecol 46:591–595, 1975
Bygdeman M, Fredricsson B, Svanborg K, Samuelsson B: The relation between fertility and prostaglandin content of seminal fluid in man. Fertil Steril 21:622–629, 1970
Kirton KT, Gutknecht GD, Bergstrom KK, Wyngarden LJ, Forbes AD: Prostaglandins and reproduction. J Reprod Med 9:266–270, 1972
Moncada S, Salmon JA, Vane JR, Whittle BJR: Formation of prostacyclin (PGI2) and its product 6-oxo-PGF1 by the gastric mucosa of several species. J Physiol (London) 275:4–5, 1977
Ahlquist DA, Duenes JA, Madson TH, Romero JC, Dozois RR, Malagelada J-R: Prostaglandin generation from gastroduodenal mucosa: Regional and species differences. Prostaglandins 24:115–125, 1982
Bennett A, Stanford IF, Stockley HL: Estimation and characterization of prostaglandins in the human gastrointestinal tract. Br J Pharmacol 61:579–586, 1977
Peskar BM: Regional distribution of prostaglandin-metabolizing enzymes in the mucosa of the human upper gastrointestinal tract. Acta Hepatogastroenterol 25:49–51, 1978
Gallavan RH Jr, Jacobson ED: Prostaglandins and the splanchnic circulation. Proc Soc Exp Biol Med 170:391–397, 1982
Robert A: Effects of prostaglandins on the stomach and the intestine. Prostaglandins 6:523–532, 1974
Jacobson ED: Comparison of prostaglandin E1 and norepinephrine on the gastric mucosal circulation. Proc Soc Exp Biol Med 113:516–519, 1970
Walus KM, Pawlik W, Konturek SJ: Prostacyclin-induced gastric mucosal vasodilation and inhibition of acid secretion in the dog. Proc Soc Exp Biol Med 163:228–232, 1980
Konturek SJ, Robert A, Hauchar AJ, Nezamis JE: Comparison of prostacyclin and prostaglandin E2 on gastric secretion, gastrin release, and mucosal blood flow in dogs. Dig Dis Sci 25:673–679, 1980
Classen M, Koch H, Bickhardt J, Topf G, Demling L: The effect of prostaglandin E1 on the pentagastrin-stimulated gastric secretion in man. Digestion 4:333–344, 1971
Horton EW, Main IHM, Thompson CJ, Wright PM: Effect of orally administered prostaglandin E1 on gastric secretion and gastrointestinal motility in man. Gut 9:655–658, 1968
Johansson BR: Oral PGE2 inhibits gastric acid secretion in man. Prostaglandins 29:143–152, 1985
Konturek SJ, Kwiecien N, Swierczek J, Oleksy J, Sito E, Robert A: Comparison of methylated prostaglandin E2 analogues given orally in the inhibition of gastric responses to pentagastrin and peptone meal in man. Gastroenterology 70:683–687, 1976
Ippoliti AF, Isenberg J, Hagiel L: Effect of oral and intravenous 16,16-dimethyl PGF2 on duodenal ulcer and Zollinger-Ellison syndrome patients. Gastroenterology 80:55–60, 1981
Konturek SJ, Tasler J, Kwiecien N, Cieszkowski M, Obtulowicz W: Mechanisms of the inhibitory action of prostaglandins on meal-induced gastric secretion. Digestion 17:281–290, 1978
Robert A: Prostaglandins and the gastrointestinal tract.In Physiology of the Gastrointestinal Tract. LR Johnson (ed). New York, Raven Press, 1981, pp 1407–1434
Nylander B, Andersson S: Gastric secretory inhibition induced by three methyl analogs of prostaglandin E2 administered intragastrically to man. Scand J Gastroenterol 9:751–758, 1974
Levine RA, Kohen KR, Schwartzek EH, Ramsay CE: prostaglandin E2-histamine interactions on cAMP, cGMP and acid production in isolated fundic glands. Am J Physiol 242:G21-G29, 1982
Soll AH: Specific inhibition by prostaglandins E2 and I2 of histamine-stimulated [14C]aminopyrine accumulation and cyclic AMP generation by isolated canine parietal cells. J Clin Invest 65:1222–1229, 1980
Saffouri B, Weir GC, Bitar KN, Makhlouf GM: Gastrin and somatostatin secretion by perfused rat stomach: Functional linkage of antral peptide. Am J Physiol 238:G495-G498, 1980
Bickel M, Kauffman GL: Gastric gel mucus thickness: Effect of distension, 16,16-dimethyl prostaglandin E2, and carbenoxolone. Gastroenterology 80:770–775, 1981
Johansson C, Kollberg B: Stimulation by intragastrically administered E2 prostaglandins of human gastric mucus output. Eur J Clin Invest 9:229–232, 1978
Ruppin H, Person B, Robert A, Domschke W: Gastric cytoprotection in man by prostaglandin E2. Scand J Gastroenterol 16:647–652, 1981
Flemstrom G, Garner A: Gastroduodenal HCO3 transport: Characteristics and proposed role in acidity regulation and mucosal protection. Am J Physiol 242:G183-G193, 1982
Konturek SJ, Bilski J, Tasler J, Kania J: Prostaglandins and alkaline secretion from oxyntic antral and duodenal mucosa of the dog. Am J Physiol 245:G539-G546, 1983
Robert A: Cytoprotection by prostaglandins. Gastroenterology 77:761–767, 1979
Konturek SJ, Brozozowski T, Piastucki I, Radecki T, Dembinski A, Dembinska-kiec A: Role of locally generated prostaglandins in adaptive gastric cytoprotection. Dig Dis Sci 27:967–971, 1982
Konturek SJ: Clinical aspects of gastric protection.In IUPHAR 9TH International Congress of Pharmacology, Proceedings. W Paton, J Mitchell, P Turner (eds). London, Macmillan Press, 1984, pp 341–344
Robert A, Nezamis JE, Lancaster C, Davis JP, Field SO, Hanchar AJ: Mild irritants prevent gastric necrosis through adaptive cytoprotection mediated by prostaglandins. Am J Physiol 245:G113-G121, 1983
Whittle BJR, Steel G: Evaluation of the protection of rat gastric mucosa by prostaglandin analogue using cellular enzyme marker and histologic techniques. Gastroenterology 88:315–327, 1985
Lichtenberger LM, Richards JE, Hills BA: Effect of 16,16-dimethyl prostaglandin E2 on the surface hydrophobicity of aspirin-treated canine gastric mucosa. Gastroenterology 88:308–314, 1985
Lichtenberger LM, Graziani LA, Dial E, Butler BD, Hills BA: Role of surface-active phospholipids in gastric cytoprotection. Science 219:1327–1329, 1983
Konturek SJ, Thor P, Pawlik W, Gustaw P, Dembinski A: Role of prostaglandins in the myoelectric, motor, and metabolic activity of the small intestine in the dog.In Motility of the Digestive Tract. M Wienbeck (ed). New York, Raven Press, 1982, pp 437–443
Robert A, Nezamis JE, Lancaster C, Hanchor AJ, Klepper MS: Enteropooling assay: A test for diarrhea produced by prostaglandins. Prostaglandins 11:809–828, 1976
Robert A: Cytoprotection and enteropooling by prostaglandins.In The Prostaglandin System. F Beri, GP Velo (eds). New York, Plenum Press, 1981, pp 393–400
Konturek SJ, Walus KM, Gustaw P: Comparison of arachidonic acid, prostacyclin and prostaglandin E2 on gastric secretion and gastric blood flow.In Gastro-Intestinal Mucosal Blood Flow. LP Fielding (ed). Edinburgh, Churchill Livingstone, 1980, pp 170–179
Gerkens JF, Gerber JG, Shand DG, Branch RA: Effect of PGI2, PGF2 and 6-keto PGF1 on canine gastric blood flow and acid secretion. Prostaglandins 16:815–823, 1978
Main IHM, Whittle BJR: The effects of E and A prostaglandins on gastric mucosal blood flow and acid secretion in the rat. Br J Pharmacol 49:428–436, 1973
Konturek SJ, Mikos E, Pawlik W, Walus K: Direct inhibition of gastric secretion and mucosal blood flow by arachidonic acid. J Physiol (London) 286:15–28, 1979
Kauffman GL Jr, Aures D, Grossman MI: Indomethacin decreases basal gastric mucosal blood flow. Gastroenterology 1165–1169, 1979
Tepperman BL, Jacobson ED: Mesenteric circulation.In Physiology of the Gastrointestinal Tract. LR Johnson (ed). New York, Raven Press, 1981, pp 1317–1336
Pawlik W, Shepherd AP, Jacobson ED: Effects of vasoactive agents on intestinal oxygen consumption and blood flow in dogs. J Clin Invest 56:484–490, 1975
Katz RL, Katz GJ: Prostaglandins-basic and clinical considerations. Anaesthesiology 40:471–493, 1974
Holmes SW, Horton EW: The identification of four prostaglandins in dog brain and their regional distribution in the central nervous system. J Physiol (London) 195:731–741, 1968
Coceani F: Prostaglandins and the central nervous system. Arch Intern Med 133:119–129, 1974
Siesjo BAK, Nilsson B: Prostaglandins and the cerebral circulation.In Prostaglandins and the Cardiovascular System. JA Oates (ed). New York, Raven Press, 1982, pp 367–380
Milton AS, Wendlandt S: A possible role for prostaglandin E1 as a modulator for temperature regulation in the central nervous system of the cat. J Physiol (London) 207:76–77, 1971
Dyerberg J, Bang HO, Hjorne B: Fatty acid composition of the plasma lipids in Greenland Eskimos. Am J Clin Nutr 28:958–966, 1975
Dyerberg J, Bang HO, Stoffersen E, Moncada S, Vane JR: Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis. Lancet 2:117–119, 1978
Crawford MA: Background to essential fatty acids and their prostanoid derivatives. Br Med Bull 39:210–213, 1983
Oliw E, Granstrom E, Anggard E: The prostaglandins and essential fatty acids.In Prostaglandins and Related Substances. C Pace-Asciak, E Granstrom (eds). New York, Elsevier Science Publishers, 1983, pp 1–44
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Konturek, S.J., Pawlik, W. Physiology and pharmacology of prostaglandins. Digest Dis Sci 31 (Suppl 2), 6S–19S (1986). https://doi.org/10.1007/BF01309317
Issue Date:
DOI: https://doi.org/10.1007/BF01309317