IUPAC_name = 5- [7-hydroxy-8- (3-hydroxyoct-1-enyl) -4-oxabicyclo [3.3.0] oct-3-ylidene] pentanoic acid
CAS_number = 35121-78-9
ATC_prefix = B01
ATC_suffix = AC09
PubChem = 114805
DrugBank = APRD00949
C=20 | H=32 | O=5
molecular_weight = 352.465 g/mol
smiles = OC(=O)CCCC=C1C [C@@H] 2 [C@@H] (/C=C/ [C@@H] (O)CCCCC) [C@H] (O)C [C@@H] 2O1
Prostacyclin (or PGI2) is a member of the family of
lipid molecules known as eicosanoids.
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.
Prostacyclin, which has a
half-lifeof seconds, is broken down into 6-keto-PGF1 which is a much weaker vasodilator.
Mode of action
Prostacyclin (PGI2) is released by healthy endothelial cells and performs its function through a
paracrinesignaling cascade that involves G protein-coupled receptors on nearby platelets and endothelial cells. The platelet Gs protein-coupled receptor ( prostacyclin receptor) is activated when it binds to PGI2. This activation, in turn, signals adenylyl cyclase to produce cAMP. cAMP goes on to inhibit any undue platelet activation (in order to promote circulation) and also counteracts any increase in cytosolic calcium levels which would result from thromboxane A2(TXA2) binding (leading to platelet activation and subsequent coagulation). PGI2 also binds to endothelial prostacyclin receptors and in the same manner raise cAMP levels in the cytosol. This cAMP then goes on to activate protein kinase A(PKA). PKA then continues the cascade by activating myosin light-chain kinasewhich leads to smooth musclerelaxation and vasodilation. Notably, PGI2 and TXA2 work as antagonists.
Prostacyclin (PGI2) chiefly prevents formation of the
plateletplug involved in primary hemostasis(a part of blood clotformation). It is also an effective vasodilator. Prostacyclin's interactions in contrast to thromboxane(TXA2), another eicosanoid, strongly suggest a mechanism of cardiovascular homeostasisbetween the two hormones in relation to vascular damage.
Synthetic prostacyclin analogues (
iloprost, cisaprost) are used intravenously, subcutaneously or by inhalation:
* as a
vasodilatorin severe Raynaud's phenomenonor ischemiaof a limb;
Its production is inhibited indirectly by NSAIDs, which inhibit the
cyclooxygenaseenzymes COX1 and COX2. These convert arachidonic acidto prostaglandin H2(PGH2), the immediate precursor of prostacyclin. Since thromboxane (an eicosanoidstimulator of platelet aggregation ) is also downstream of COX enzymes, one would think that the effect of NSAIDs would balance out. However, prostacyclin concentrations recover much faster than thromboxane levels, so aspirin administration initially has little to no effect but eventually prevents platelet aggregation (the effect of thromboxane predominates). This is explained by understanding the cells that produce each molecule, TXA2 and PGI2. Since PGI2 is primarily produced in a nucleated endothelial cell the COX inhibition by NSAID can be overcome with time by increased COX gene activation and subsequent production of more COX enzymes to catalyzethe formation of PGI2. In contrast, TXA2 is primarily released by anucleated plateles which are unable to respond to NSAID COX inhibition with additional transcriptionof the COX gene because they lack DNAmaterial necessary to perform such a task. This allows NSAIDs to result in PGI2 dominance that promotes circulation and retards thrombosis.
Essential fatty acid
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prostacyclin — [präs΄tə sī′klin] n. [< PROSTAGLANDIN + CYCL(O) + IN1] a derivative of prostaglandins that forms in the walls of blood vessels, prevents blood clots, and, usually, dilates blood vessels: cf. THROMBOXANE … English World dictionary
Prostacyclin — Strukturformel Allgemeines Freiname Epoprostenol And … Deutsch Wikipedia
prostacyclin — noun Etymology: prosta (as in prostaglandin) + cycl + 1 in Date: 1976 a prostaglandin that is a metabolite of arachidonic acid, inhibits platelet aggregation, and dilates blood vessels … New Collegiate Dictionary
prostacyclin — (= PGI2) Unstable prostaglandin released by mast cells and endothelium, a potent inhibitor of platelet aggregation; also causes vasodilation and increased vascular permeability. Release enhanced by bradykinin … Dictionary of molecular biology
prostacyclin — /pros teuh suy klin/, n. Biochem. a prostaglandin, C20H32O5, that specifically inhibits the formation of blood clots. [1975 80; PROSTA(TE) + CYCL(IC) + IN2, on the model of PROSTAGLANDIN] * * * … Universalium
prostacyclin — noun A prostaglandin produced in the walls of blood vessels; it acts as a vasodilator and inhibits the aggregation of platelets … Wiktionary
prostacyclin — A potent natural inhibitor of platelet aggregation and a powerful vasodilator. SYN: epoprostenol, epoprostenol sodium. * * * pros·ta·cy·clin .präs tə sī klən n a prostaglandin that is a metabolite of arachidonic acid, inhibits aggregation of… … Medical dictionary
Prostacyclin — Pro|s|ta|cy|c|lin [↑ Prostaglandin, ↑ cyclo u. ↑ in (3)], das; s, e; Abk.: PGI2, PGX; S: Prostazyklin: eine blutdrucksenkende u. die Thrombozytenaggregation hemmende Epoxydihydroxyprostadiensäure, die bei der Prostaglandin Biosynthese aus einer… … Universal-Lexikon
prostacyclin — [ˌprɒstə sʌɪklɪn] noun Biochemistry a compound of the prostaglandin type produced in arterial walls, which functions as an anticoagulant and vasodilator. Origin 1970s: from prostaglandin + cyclic + in1 … English new terms dictionary
prostacyclin — pros·ta·cy·clin … English syllables