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Gene Review

Ptgs1  -  prostaglandin-endoperoxide synthase 1

Rattus norvegicus

Synonyms: COX-1, Cox-1, Cox-3, Cox1, Cox3, ...
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Disease relevance of Ptgs1

  • Prostaglandins (PGs) generated by the enzyme cyclooxygenase (COX) have been implicated in the pathological renal hemodynamics and structural alterations in diabetes mellitus, but the role of individual COX isoenzymes in diabetic nephropathy remains unknown [1].
  • BACKGROUND & AIMS: The critical role of cyclooxygenase (COX) products in maintenance of renal function in cirrhosis with ascites discourages the use of nonsteroidal anti-inflammatory drugs in this disease [2].
  • This study evaluated the relationship between inflammatory mediators, COX expression, and pathological changes in experimental alcoholic liver disease [3].
  • Epidemiological and laboratory studies suggest that nonsteroidal antiinflammatory drugs reduce the risk of colon cancer and that the inhibition of colon carcinogenesis is mediated through modulation of prostaglandin production by cyclooxygenase (COX) isozymes (COX-1 and -2) [4].
  • In addition, a nonselective (acetylsalicylic acid) or selective cyclooxygenase (COX) 1 inhibitor (SC-560) completely abrogated the 8-iso-PGF(2alpha) and PGF(2alpha) formation in kidneys subjected to ischemia [5].

Psychiatry related information on Ptgs1

  • The effects of different COX and NOS inhibitors on the intestinal motor activity were tested. mRNA expression of COX-1 was not modified by inflammation, whereas mRNA expression of neuronal NOS was reduced in all indomethacin-treated rats [6].
  • In the current study, we sought to determine the role of COX isoenzymes after laparotomy, examining spontaneous exploratory behavior rather than withdrawal reflexes [7].
  • In this study, we investigated the therapeutic potential for Alzheimer's disease of mefenamic acid, a commonly used NSAID that is a cyclooxygenase-1 and 2 inhibitor with only moderate anti-inflammatory properties [8].
  • Extending the current view on the treatment of drug dependence, these results indicate that endocannabinoid-activating substances as well as cyclooxygenase inhibitors may be promising as antirelapse agents [9].
  • The above results indicate that in rats subjected to a prolonged period of dietary restriction, the uterine glycogen becomes responsive to the effects of cyclooxygenase and lipoxygenase inhibitors, suggesting the operation of some regulatory mechanism during critical periods of nutrition [10].

High impact information on Ptgs1


Chemical compound and disease context of Ptgs1


Biological context of Ptgs1


Anatomical context of Ptgs1


Associations of Ptgs1 with chemical compounds

  • These eicosanoids, formed by cyclooxygenase-dependent metabolism of arachidonic acid, are important physiologic mediators of renal glomerular hemodynamics and tubular sodium and water reabsorption [27].
  • Pathological analyses and measurements of lipid peroxidation, tumor necrosis factor (TNF)-alpha, COX-1 and COX-2 messenger RNA (mRNA), endotoxin, and liver and plasma thromboxane were performed [3].
  • To provide an understanding of the mechanism(s) of dietary fat-induced modulation of colon tumor development, we have analyzed the expression of cyclooxygenase (COX), an enzyme that catalyzes the metabolism of omega-3 and omega-6 polyunsaturated fatty acids in a critical step in prostaglandin biosynthesis [23].
  • Serum-treated SMC also generated greater amounts of cyclooxygenase-dependent metabolites than quiescent SMC as evidenced by marked increases in prostaglandin E2 content in conditioned media [25].
  • Both the Cox-1 mRNA, quantified in the whole lung homogenate, and the cellular localization of Cox-1 were unchanged in response to LPS [28].

Physical interactions of Ptgs1

  • The results indicate that ADM interacts with COX to yield prostanoids, which mediate its negative inotropic effect in LPS-treated rat ventricular myocytes [29].

Regulatory relationships of Ptgs1


Other interactions of Ptgs1

  • Rats selected at either active or reactive phases and from 2 to 60 days after indomethacin treatment were used. mRNA expression of both constitutive and inducible NOS and COX isoforms in each phase was evaluated by RT-PCR and cellular enzyme localization by immunohistochemistry [6].
  • These results suggest that COX-1 and cNOS play as the respective key enzyme responsible for producing PG and NO following the duodenal acidification, both of which are involved in the mechanism for the acid-induced HCO3- secretion in the duodenum [35].
  • The mRNA levels of cPLA2, COX-2 and mPGES-1 in the bladder papilloma and TCC were significantly higher than those in normal bladder (P<0.01), while the mRNA levels of COX-1 and mPGES-2 in TCC were unchanged compared with normal bladder [36].
  • Laparotomy stimulated HO activity, whereas gut manipulation led to an excessive constitutive NOS stimulation accompanied by augmented prostanoid synthesis by COX-1 [37].
  • Lipopolysaccharide-induced increase of prostaglandin E(2) is mediated by inducible nitric oxide synthase activation of the constitutive cyclooxygenase and induction of membrane-associated prostaglandin E synthase [38].

Analytical, diagnostic and therapeutic context of Ptgs1


  1. Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes. Komers, R., Lindsley, J.N., Oyama, T.T., Schutzer, W.E., Reed, J.F., Mader, S.L., Anderson, S. J. Clin. Invest. (2001) [Pubmed]
  2. Selective inhibition of cyclooxygenase 2 spares renal function and prostaglandin synthesis in cirrhotic rats with ascites. Bosch-Marcè, M., Clària, J., Titos, E., Masferrer, J.L., Altuna, R., Poo, J.L., Jiménez, W., Arroyo, V., Rivera, F., Rodés, J. Gastroenterology (1999) [Pubmed]
  3. Enhanced cyclooxygenase-2 gene expression in alcoholic liver disease in the rat. Nanji, A.A., Miao, L., Thomas, P., Rahemtulla, A., Khwaja, S., Zhao, S., Peters, D., Tahan, S.R., Dannenberg, A.J. Gastroenterology (1997) [Pubmed]
  4. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Kawamori, T., Rao, C.V., Seibert, K., Reddy, B.S. Cancer Res. (1998) [Pubmed]
  5. Cyclooxygenase 1-dependent production of F2-isoprostane and changes in redox status during warm renal ischemia-reperfusion. Favreau, F., Petit-Paris, I., Hauet, T., Dutheil, D., Papet, Y., Mauco, G., Tallineau, C. Free Radic. Biol. Med. (2004) [Pubmed]
  6. Cyclical upregulated iNOS and long-term downregulated nNOS are the bases for relapse and quiescent phases in a rat model of IBD. Porras, M., Martín, M.T., Torres, R., Vergara, P. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  7. Intrathecal administration of a cylcooxygenase-1, but not a cyclooxygenase-2 inhibitor, reverses the effects of laparotomy on exploratory activity in rats. Martin, T.J., Buechler, N.L., Eisenach, J.C. Anesth. Analg. (2006) [Pubmed]
  8. Mefenamic acid shows neuroprotective effects and improves cognitive impairment in in vitro and in vivo Alzheimer's disease models. Joo, Y., Kim, H.S., Woo, R.S., Park, C.H., Shin, K.Y., Lee, J.P., Chang, K.A., Kim, S., Suh, Y.H. Mol. Pharmacol. (2006) [Pubmed]
  9. Endocannabinoid system modulates relapse to methamphetamine seeking: possible mediation by the arachidonic acid cascade. Anggadiredja, K., Nakamichi, M., Hiranita, T., Tanaka, H., Shoyama, Y., Watanabe, S., Yamamoto, T. Neuropsychopharmacology (2004) [Pubmed]
  10. Effect of chronic underfeeding on uterine glycogen of rats. Influence of indomethacin and nordihydroguaiaretic acid. López, M., González, E.T., Sterin, A.B., Goldraij, A. Prostaglandins Leukot. Essent. Fatty Acids (1991) [Pubmed]
  11. Inducible cyclooxygenase may have anti-inflammatory properties. Gilroy, D.W., Colville-Nash, P.R., Willis, D., Chivers, J., Paul-Clark, M.J., Willoughby, D.A. Nat. Med. (1999) [Pubmed]
  12. How opioids inhibit GABA-mediated neurotransmission. Vaughan, C.W., Ingram, S.L., Connor, M.A., Christie, M.J. Nature (1997) [Pubmed]
  13. G-protein beta gamma-subunits activate the cardiac muscarinic K+-channel via phospholipase A2. Kim, D., Lewis, D.L., Graziadei, L., Neer, E.J., Bar-Sagi, D., Clapham, D.E. Nature (1989) [Pubmed]
  14. Potent ulcerogenic actions of platelet-activating factor on the stomach. Rosam, A.C., Wallace, J.L., Whittle, B.J. Nature (1986) [Pubmed]
  15. Macrocortin: a polypeptide causing the anti-phospholipase effect of glucocorticoids. Blackwell, G.J., Carnuccio, R., Di Rosa, M., Flower, R.J., Parente, L., Persico, P. Nature (1980) [Pubmed]
  16. Effects of inhibition of prostaglandin endoperoxide synthase-2 in chronic gastro-intestinal ulcer models in rats. Schmassmann, A., Peskar, B.M., Stettler, C., Netzer, P., Stroff, T., Flogerzi, B., Halter, F. Br. J. Pharmacol. (1998) [Pubmed]
  17. Myocardial protection by pioglitazone, atorvastatin, and their combination: mechanisms and possible interactions. Ye, Y., Lin, Y., Atar, S., Huang, M.H., Perez-Polo, J.R., Uretsky, B.F., Birnbaum, Y. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  18. Role of cyclooxygenase-2 in the healing of gastric ulcers in rats. Shigeta, J., Takahashi, S., Okabe, S. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
  19. Differential role of cyclooxygenase 1 and 2 isoforms in the modulation of colonic neuromuscular function in experimental inflammation. Fornai, M., Blandizzi, C., Antonioli, L., Colucci, R., Bernardini, N., Segnani, C., De Ponti, F., Del Tacca, M. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  20. Cyclooxygenase inhibitors attenuate bradykinin-induced vasoconstriction in septic isolated rat lungs. Fischer, L.G., Hollmann, M.W., Horstman, D.J., Rich, G.F. Anesth. Analg. (2000) [Pubmed]
  21. Oxidative damage of cardiomyocytes is limited by extracellular regulated kinases 1/2-mediated induction of cyclooxygenase-2. Adderley, S.R., Fitzgerald, D.J. J. Biol. Chem. (1999) [Pubmed]
  22. Cyclooxygenase-1 behaves as a delayed response gene in PC12 cells differentiated by nerve growth factor. Kaplan, M.D., Olschowka, J.A., O'Banion, M.K. J. Biol. Chem. (1997) [Pubmed]
  23. Dietary fat and colon cancer: modulation of cyclooxygenase-2 by types and amount of dietary fat during the postinitiation stage of colon carcinogenesis. Singh, J., Hamid, R., Reddy, B.S. Cancer Res. (1997) [Pubmed]
  24. Regulation of the expression of cyclooxygenase-2 by nitric oxide in rat peritoneal macrophages. Habib, A., Bernard, C., Lebret, M., Creminon, C., Esposito, B., Tedgui, A., Maclouf, J. J. Immunol. (1997) [Pubmed]
  25. Induction of cyclooxygenase-2 in rat vascular smooth muscle cells in vitro and in vivo. Pritchard, K.A., O'Banion, M.K., Miano, J.M., Vlasic, N., Bhatia, U.G., Young, D.A., Stemerman, M.B. J. Biol. Chem. (1994) [Pubmed]
  26. Elevated levels of cyclooxygenase-2 in antigen-stimulated mast cells is associated with minimal activation of p38 mitogen-activated protein kinase. Hundley, T.R., Prasad, A.R., Beaven, M.A. J. Immunol. (2001) [Pubmed]
  27. Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction. Harris, R.C., McKanna, J.A., Akai, Y., Jacobson, H.R., Dubois, R.N., Breyer, M.D. J. Clin. Invest. (1994) [Pubmed]
  28. Rat pulmonary cyclooxygenase-2 expression in response to endotoxin challenge: differential regulation in the various types of cells in the lung. Ermert, L., Ermert, M., Merkle, M., Goppelt-Struebe, M., Duncker, H.R., Grimminger, F., Seeger, W. Am. J. Pathol. (2000) [Pubmed]
  29. Role of cyclooxygenase in ventricular effects of adrenomedullin: is adrenomedullin a double-edged sword in sepsis? Mittra, S., Hyvelin, J.M., Shan, Q., Tang, F., Bourreau, J.P. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  30. Up-regulation of cyclooxygenase-2 by inhibition of cyclooxygenase-1: a key to nonsteroidal anti-inflammatory drug-induced intestinal damage. Tanaka, A., Hase, S., Miyazawa, T., Takeuchi, K. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  31. The role of cyclooxygenase-1 and cyclooxygenase-2 in lipopolysaccharide and interleukin-1 stimulated enterocyte prostanoid formation. Longo, W.E., Damore, L.J., Mazuski, J.E., Smith, G.S., Panesar, N., Kaminski, D.L. Mediators of inflammation. (1998) [Pubmed]
  32. Endothelin regulates PGE2 formation in rat mesangial cells through induction of prostaglandin endoperoxide synthase-2. Coroneos, E., Kester, M., Thomas, P., Dunn, M.J. Adv. Prostaglandin Thromboxane Leukot. Res. (1995) [Pubmed]
  33. Role of interleukin 1 in the regulation of cyclooxygenase gene expression in rat endometrial stromal cells. Bany, B.M., Kennedy, T.G. J. Reprod. Fertil. (1999) [Pubmed]
  34. Cyclooxygenase metabolites mediate glomerular monocyte chemoattractant protein-1 formation and monocyte recruitment in experimental glomerulonephritis. Schneider, A., Harendza, S., Zahner, G., Jocks, T., Wenzel, U., Wolf, G., Thaiss, F., Helmchen, U., Stahl, R.A. Kidney Int. (1999) [Pubmed]
  35. COX and NOS isoforms involved in acid-induced duodenal bicarbonate secretion in rats. Takeuchi, K., Kagawa, S., Mimaki, H., Aoi, M., Kawauchi, S. Dig. Dis. Sci. (2002) [Pubmed]
  36. Elevated prostaglandin E2 level via cPLA2--COX-2--mPGES-1 pathway involved in bladder carcinogenesis induced by terephthalic acid-calculi in Wistar rats. Shi, Y., Cui, L., Dai, G., Chen, J., Pan, H., Song, L., Cheng, S., Wang, X. Prostaglandins Leukot. Essent. Fatty Acids (2006) [Pubmed]
  37. The role and interactions of nitric oxide (NO), carbon monoxide (CO), and prostanoids in the pathogenesis of postoperative ileus in rats. Korolkiewicz, R.P., Sein-Anand, J., Ruczyński, J., Rekowski, P., Bieniaszewski, L., Chodorowski, Z., Petrusewicz, J., Ujda, M., Dabkowski, J., Bitel, M., Kato, S., Takeuchi, K. J. Gastrointest. Surg. (2004) [Pubmed]
  38. Lipopolysaccharide-induced increase of prostaglandin E(2) is mediated by inducible nitric oxide synthase activation of the constitutive cyclooxygenase and induction of membrane-associated prostaglandin E synthase. Devaux, Y., Seguin, C., Grosjean, S., de Talancé, N., Camaeti, V., Burlet, A., Zannad, F., Meistelman, C., Mertes, P.M., Longrois, D. J. Immunol. (2001) [Pubmed]
  39. 24R,25-(OH)(2)D(3) mediates its membrane receptor-dependent effects on protein kinase C and alkaline phosphatase via phospholipase A(2) and cyclooxygenase-1 but not cyclooxygenase-2 in growth plate chondrocytes. Schwartz, Z., Sylvia, V.L., Del Toro, F., Hardin, R.R., Dean, D.D., Boyan, B.D. J. Cell. Physiol. (2000) [Pubmed]
  40. Antithrombin reduces ischemia/reperfusion-induced liver injury in rats by activation of cyclooxygenase-1. Harada, N., Okajima, K., Uchiba, M., Kushimoto, S., Isobe, H. Thromb. Haemost. (2004) [Pubmed]
  41. Cyclooxygenase-1 in the spinal cord plays an important role in postoperative pain. Zhu, X., Conklin, D., Eisenach, J.C. Pain (2003) [Pubmed]
  42. Rat colorectal tumours treated with a range of non-steroidal anti-inflammatory drugs show altered cyclooxygenase-2 and cyclooxygenase-1 splice variant mRNA expression levels. Vogiagis, D., Brown, W., Glare, E.M., O'Brien, P.E. Carcinogenesis (2001) [Pubmed]
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