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Research ArticleArticle

Modulation of Prostaglandin Biosynthesis by Nitric Oxide and Nitric Oxide Donors

Vincenzo Mollace, Carolina Muscoli, Emanuela Masini, Salvatore Cuzzocrea and Daniela Salvemini
Pharmacological Reviews June 2005, 57 (2) 217-252; DOI: stonel.info/10.1124/pr.57.2.1
Vincenzo Mollace
Faculty of Pharmacy, University of Catanzaro “Magna Graecia”, Roccelletta di Borgia, Catanzaro, Italy (V.M., C.M.); Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy (E.M.); Institute of Pharmacology, University of Messina, Messina, Italy (S.C.); and Department of Pharmacological and Physiological Science, School of Medicine, St. Louis University, St. Louis, Missouri (D.S.)
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Carolina Muscoli
Faculty of Pharmacy, University of Catanzaro “Magna Graecia”, Roccelletta di Borgia, Catanzaro, Italy (V.M., C.M.); Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy (E.M.); Institute of Pharmacology, University of Messina, Messina, Italy (S.C.); and Department of Pharmacological and Physiological Science, School of Medicine, St. Louis University, St. Louis, Missouri (D.S.)
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Emanuela Masini
Faculty of Pharmacy, University of Catanzaro “Magna Graecia”, Roccelletta di Borgia, Catanzaro, Italy (V.M., C.M.); Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy (E.M.); Institute of Pharmacology, University of Messina, Messina, Italy (S.C.); and Department of Pharmacological and Physiological Science, School of Medicine, St. Louis University, St. Louis, Missouri (D.S.)
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Salvatore Cuzzocrea
Faculty of Pharmacy, University of Catanzaro “Magna Graecia”, Roccelletta di Borgia, Catanzaro, Italy (V.M., C.M.); Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy (E.M.); Institute of Pharmacology, University of Messina, Messina, Italy (S.C.); and Department of Pharmacological and Physiological Science, School of Medicine, St. Louis University, St. Louis, Missouri (D.S.)
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Daniela Salvemini
Faculty of Pharmacy, University of Catanzaro “Magna Graecia”, Roccelletta di Borgia, Catanzaro, Italy (V.M., C.M.); Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy (E.M.); Institute of Pharmacology, University of Messina, Messina, Italy (S.C.); and Department of Pharmacological and Physiological Science, School of Medicine, St. Louis University, St. Louis, Missouri (D.S.)
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Abstract

The biosynthesis and release of nitric oxide (NO) and prostaglandins (PGs) share a number of similarities. Two major forms of nitric-oxide synthase (NOS) and cyclooxygenase (COX) enzymes have been identified to date. Under normal circumstances, the constitutive isoforms of these enzymes (constitutive NOS and COX-1) are found in virtually all organs. Their presence accounts for the regulation of several important physiological effects (e.g. antiplatelet activity, vasodilation, and cytoprotection). On the other hand, in inflammatory setting, the inducible isoforms of these enzymes (inducible NOS and COX-2) are detected in a variety of cells, resulting in the production of large amounts of proinflammatory and cytotoxic NO and PGs. The release of NO and PGs by the inducible isoforms of NOS and COX has been associated with the pathological roles of these mediators in disease states as evidenced by the use of selective inhibitors. An important link between the NOS and COX pathways was made in 1993 by Salvemini and coworkers when they demonstrated that the enhanced release of PGs, which follows inflammatory mechanisms, was nearly entirely driven by NO. Such studies raised the possibility that COX enzymes represent important endogenous “receptor” targets for modulating the multifaceted roles of NO. Since then, numerous papers have been published extending the observation across various cellular systems and animal models of disease. Furthermore, other studies have highlighted the importance of such interaction in physiology as well as in the mechanism of action of drugs such as organic nitrates. More importantly, mechanisticstudies of how NO switches on/off the PG/COX pathway have been undertaken and additional pathways through which NO modulates prostaglandin production unraveled. On the other hand, NO donors conjugated with COX inhibitors have recently found new interest in the understanding of NO/COX reciprocal interaction and potential clinical use. The purpose of this article is to cover the advances which have occurred over the years, and in particular, to summarize experimental data that outline how the discovery that NO modulates prostaglandin production has impacted and extended our understanding of these two systems in physiopathological events.

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Pharmacological Reviews: 57 (2)
Pharmacological Reviews
Vol. 57, Issue 2
1 Jun 2005
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Research ArticleArticle

Modulation of Prostaglandin Biosynthesis by Nitric Oxide and Nitric Oxide Donors

Vincenzo Mollace, Carolina Muscoli, Emanuela Masini, Salvatore Cuzzocrea and Daniela Salvemini
Pharmacological Reviews June 1, 2005, 57 (2) 217-252; DOI: stonel.info/10.1124/pr.57.2.1

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Research ArticleArticle

Modulation of Prostaglandin Biosynthesis by Nitric Oxide and Nitric Oxide Donors

Vincenzo Mollace, Carolina Muscoli, Emanuela Masini, Salvatore Cuzzocrea and Daniela Salvemini
Pharmacological Reviews June 1, 2005, 57 (2) 217-252; DOI: stonel.info/10.1124/pr.57.2.1
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    • Abstract
    • I. Introduction
    • II. The Prostaglandin Biosynthetic Pathway
    • III. Nitric Oxide and Nitric Oxide Donors
    • IV. Interaction between Nitric Oxide and Prostaglandin Biosynthesis
    • V. Perspectives and Concluding Remarks
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