Prostacyclin

Information about Prostacyclin

Prostacyclin is a member of the family of lipid molecules known as eicosanoids. Epoprostenol (brand name Flolan) is a synthetic form of prostacyclin, approved by the FDA as a medicine in 1995. Epoprostenol was developed by GlaxoSmithKline and licensed to Myogen, which was subsequently acquired by Gilead Sciences. Flolan is marketed in the United States by Gilead Sciences and elsewhere by GlaxoSmithKline.

Production

It is produced in endothelial cells from prostaglandin H₂ (PGH₂) by the action of the enzyme prostacyclin synthase. Although prostacyclin is considered an independent mediator, it is called PGI₂ (prostaglandin I₂) in eicosanoid nomenclature, and is a member of the prostanoids (together with the prostaglandins and thromboxane).

The series-3 prostaglandin PGH₃ also follows the prostacyclin synthase pathway, yielding another prostacyclin, PGI₃.(Fischer, 1985) The unqualified term 'prostacyclin' usually refers to PGI₂. PGI₂ is derived from the ω-6 arachidonic acid. PGI₃ is derived from the ω-3 EPA.

Eicosanoid synthesis. (Prostacyclin near bottom center.)

Mode of action

Prostacyclin acts chiefly to prevent platelet formation and clumping involved in blood clotting. It is also an effective vasodilator. Prostacyclin's interactions in contrast to thromboxane, another eicosanoid, strongly suggest a mechanism of cardiovascular homeostasis between the two hormones in relation to vascular damage.

Pharmacology

Synthetic prostacyclin analogues (iloprost, cisaprost) are used intravenously, subcutaneously or by inhalation:

as a vasodilator in severe Raynaud's phenomenon or ischemia of a limb;
in pulmonary hypertension.

Its production is inhibited indirectly by NSAIDs, which inhibit the cyclooxygenase enzymes COX1 and COX2. These convert arachidonic acid to PGH₂, the immediate precursor of prostacyclin.

References

Dorlands Medical Dictionary. epoprostenol. Retrieved on February 10, 2006.
Fischer S, Weber PC (1985). "Thromboxane (TX)A3 and prostaglandin (PG)I3 are formed in man after dietary eicosapentaenoic acid: identification and quantification by capillary gas chromatography-electron impact mass spectrometry". Biomed. Mass Spectrom. 12 (9): 470-6. PMID 2996649.

• • [ e] Antithrombotics (thrombolytics, anticoagulants and antiplatelet drugs) (B01)
Vitamin K antagonists	Acenocoumarol • Clorindione • Coumatetralyl • Dicumarol (Dicoumarol) • Diphenadione • Ethyl biscoumacetate • Phenprocoumon • Phenindione • Tioclomarol • Warfarin
Heparin group	Antithrombin III • Danaparoid • Heparin • Sulodexide • low molecular weight heparin (Bemiparin, Dalteparin, Enoxaparin, Nadroparin, Parnaparin, Reviparin, Tinzaparin)
Glycoprotein IIb/IIIa inhibitors	Abciximab • Eptifibatide • Tirofiban
Other platelet aggregation inhibitors	Acetylsalicylic acid/Aspirin • Aloxiprin • Ditazole • Carbasalate calcium • Cloricromen • Clopidogrel • Dipyridamole • Indobufen • Picotamide • Prasugrel • Ticlopidine • Triflusal • prostaglandin analogue (Beraprost, Prostacyclin, Iloprost, Treprostinil)
Enzymes	plasminogen activators (Alteplase/Reteplase/Tenecteplase, Streptokinase, Urokinase/Saruplase, Anistreplase) • other serine endopeptidases (Ancrod, Drotrecogin alfa/Protein C, Fibrinolysin) • Brinase
Direct thrombin inhibitors	Argatroban • Bivalirudin • Dabigatran • Desirudin • Hirudin • Lepirudin • Melagatran • Ximelagatran
Other antithrombotics	Defibrotide • Dermatan sulfate • Fondaparinux • Rivaroxaban
Non-medicinal	Citrate • EDTA • Oxalate

• • [ e] Medications used in the management of pulmonary arterial hypertension (B01, C02)
Prostacyclin analogues	Beraprost, Epoprostenol, Iloprost, Treprostinil
Endothelin receptor antagonists	Ambrisentan, Bosentan, Sitaxsentan
PDE5 inhibitors	Sildenafil, Tadalafil
Adjunctive therapy	Calcium channel blockers, Diuretics, Digoxin, Oxygen therapy, Warfarin

• • [ e] Eicosanoids: prostaglandins
Endogenous/series 2	D2 - E2 (Dinoprostone) - H2 - I2 (Prostacyclin)
Prostaglandin analogues	Alprostadil - Beraprost - Bimatoprost - Carboprost - Enprostil - Iloprost - Latanoprost - Misoprostol - Travoprost - Treprostinil

Lipids can be broadly defined as any fat-soluble (hydrophobic), naturally-occurring molecules. The term is more-specifically used to refer to fatty-acids and their derivatives (including tri-, di-, and monoglycerides and phospholipids) as well as other fat-soluble sterol-containing
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molecule is defined as a sufficiently stable electrically neutral group of at least two atoms in a definite arrangement held together by strong chemical bonds.^[1]^[2] In organic chemistry and biochemistry, the term molecule
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In biochemistry, eicosanoids are signaling molecules derived from omega-3 (ω-3) or omega-6 (ω-6) fats. They exert complex control over many bodily systems, mainly in inflammation or immunity, and as messengers in the central nervous system.
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Food and Drug Administration (FDA) is an agency of the United States Department of Health and Human Services and is responsible the safety regulation of most types of foods, dietary supplements, drugs, vaccines, biological medical products, blood products, medical devices,
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GlaxoSmithKline

Public (LSE: GSK
NYSE: GSK )
Founded 2000, by merger of Glaxo Wellcome and SmithKline Beecham
Headquarters London, England, UK

Key people Sir Chris Gent, Chairman
Dr Jean-Pierre Garnier, Chief Executive
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Gilead Sciences

Public NASDAQ: GILD
Founded Foster City, California (1987)
Headquarters Foster City, California

Key people John Martin, President and Chief Executive Officer
Industry Healthcare, Biotechnology, Pharmaceutical company
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endothelium is the thin layer of cells that line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. Endothelial cells line the entire circulatory system, from the heart to the smallest capillary.
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prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring.
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Enzymes are proteins that catalyze (i.e. accelerate) chemical reactions.^[1] In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, the products.
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Prostacyclin synthase is an enzyme involved in prostacyclin synthesis.

External links

MeSH prostacyclin+synthetase

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Prostanoid is the term used to describe a subclass of eicosanoids consisting of: the prostaglandins (mediators of inflammatory and anaphylactic reactions), the thromboxanes (mediators of vasoconstriction) and the prostacyclins (active in the resolution phase of inflammation.
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Thromboxane is a member of the family of lipids known as eicosanoids. The two major thromboxanes are thromboxane A2 and thromboxane B2.

Thromboxane is named for its role in clot formation (thrombosis).
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Arachidonic acid (AA) is an omega-6 fatty acid 20:4(ω-6). It is the counterpart to the saturated arachidic acid found in peanut oil, (L. arachis – peanut.
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Eicosapentaenoic acid (EPA or also icosapentaenoic acid) is an omega-3 fatty acid. In physiological literature, it is given the name 20:5(n-3). It also has the trivial name timnodonic acid.
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Platelets, or thrombocytes, are the cell fragments circulating in the blood that are involved in the cellular mechanisms of primary hemostasis leading to the formation of blood clots.
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thrombus, or blood clot, is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e. clotting factors).
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A vasodilator is a drug or chemical that relaxes the smooth muscle in blood vessels, which causes them to dilate. Dilation of arterial blood vessels (mainly arterioles) lead to a decrease in blood pressure.
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Homeostasis is the property of either an open system or a closed system, especially a living organism, to regulate the state of its internal environment so as to maintain a stable, constant condition.
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The blood vessels are part of the cardiovascular system and function to transport blood throughout the body. The most important types, arteries and veins, carry blood away from or towards the heart, respectively.
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Iloprost, an inhalation solution, is sold under the name Ventavis® and is used to treat pulmonary arterial hypertension (PAH). It was developed by the pharmaceutical company Schering AG and is marketed by Schering AG in Europe and Actelion Pharmaceuticals in the USA.
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MeSH D011928 Raynaud's phenomenon (RAY-noz), in medicine, is a vasospastic disorder causing discoloration of the fingers, toes, and occasionally other extremities, named for French physician Maurice Raynaud (1834 - 1881).
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In medicine, ischemia (Greek ισχαιμία, isch- is restriction, hema or haema is blood) is a restriction in blood supply
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MeSH D006976 In medicine, pulmonary hypertension (PH) is an increase in blood pressure in the pulmonary artery or lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion.
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Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAIDs, are drugs with analgesic, antipyretic and anti-inflammatory effects - they reduce pain, fever and inflammation.
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Identifiers
Symbol PTGS2

Entrez 5743
HUGO 9605
OMIM 600262

RefSeq NM_000963
UniProt P35354
Other data
EC number 1.14.99.1
Locus Chr. 1 q25.2-25.3 Cyclooxygenase (COX) is an enzyme (EC 1.14.99.
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