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E1 - Alprostadil

I2 - Prostacyclin A 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. They are mediators and have a variety of strong physiological effects, such as regulating the contraction and relaxation of smooth muscle tissue.[1] Prostaglandins are not hormones, but autocrine or paracrine, which are locally acting messenger molecules. They differ from hormones in that they are not produced at a discrete site but in many places throughout the human body. Also, their target cells are present in the immediate vicinity of the site of their secretion (of which there are many). The prostaglandins, together with the thromboxanes and prostacyclins, form the prostanoid class of fatty acid derivatives, a subclass of eicosanoids.

2 Prostaglandin E synthase  2. (In fact.[4] an achievement for which he was awarded the Japan Prize in 1989.1 Inhibition o 5. The first total syntheses of prostaglandin F2α and prostaglandin E2 were reported by E.2.Contents [hide] • • • • • • • 1 History and name 2 Biochemistry o 2.[3] it was believed to be part of the prostatic secretions. Bergström.1 Cyclooxygenases  2.2 Release of prostaglandins from the cell  2.2. J. Samuelsson and John R.1 Biosynthesis o 2.2 Clinical uses 6 References 7 External links [edit] History and name The name prostaglandin derives from the prostate gland. [edit] Biochemistry [edit] Biosynthesis .3 Other terminal prostaglandin synthases 3 Function 4 Types 5 Role in pharmacology o 5. When prostaglandin was first isolated from seminal fluid in 1935 by the Swedish physiologist Ulf von Euler. it was determined that aspirin-like drugs could inhibit the synthesis of prostaglandins.[2] and independently by M. Corey in 1969. It was later shown that many other tissues secrete prostaglandins for various functions. Goldblatt. The biochemists Sune K.2. prostaglandins are produced by the seminal vesicles). Bengt I. In 1971. Vane jointly received the 1982 Nobel Prize in Physiology or Medicine for their research on prostaglandins.W.

a member of the ATP-binding cassette transporter superfamily.Biosynthesis of eicosanoids. An intermediate is created from phospholipase-A2. They are synthesized in the cell from the essential fatty acids[5] (EFAs). The cyclooxygenase pathway produces thromboxane. The lipoxygenase enzyme pathway is inactive in leukocytes and in macrophages and synthesizes leukotrienes. ABCC4). prostacyclin and prostaglandin D. endothelium. They are autocrine and paracrine lipid mediators that act upon platelets. then brought out of one of either the cyclooxygenase pathway or the lipoxygenase pathway to form either prostaglandin and thromboxane or leukotriene respectively. (series-2) Prostaglandins are found in most tissues and organs. namely the multidrug resistance protein 4 (MRP4. They are produced by all nucleated cells except lymphocytes. The release of prostaglandin has now also been shown to be mediated by a specific transporter. E and F. which mediates the cellular uptake of prostaglandin. demonstrated that diffusion alone cannot explain the penetration of prostaglandin through the cellular membrane. SLCO2A1). The discovery of the prostaglandin transporter (PGT. uterine and mast cells. Name Gamma-linolenic acid (GLA) via DGLA Arachidonic acid (AA) Eicosapentaenoic acid (EPA) EFA Type ω-6 ω-6 ω-3 Series series-1 series-2 series-3 [edit] Release of prostaglandins from the cell Prostaglandins were originally believed to leave the cells via passive diffusion because of their high lipophilicity. Whether MRP4 is the only transporter releasing prostaglandins from the cells is still unclear. [edit] Cyclooxygenases .

The classic dogma is as follows: • • COX-1 is responsible for the baseline levels of prostaglandins. A thromboxane synthase (TxAS) has also been identified. prostacyclin (PGI2) synthase (PGIS) converts PGH2 into PGI2. These receptors are termed DP1-2. This enzyme has recently been crystallyzed in complex with PGD2[6] and bimatoprost[7] (a synthetic analogue of PGF2α). prostaglandin levels are increased by COX-2 in scenarios of inflammation.11β-PGF2α. Prostaglandin F synthase (PGFS) catalyzes the formation of 9α.g. microsomal prostaglandin E synthase-1 emerges as a key enzyme in the formation of PGE2. G-protein-coupled receptors. DGLA or EPA by cyclooxygenases (COX-1 and COX-2) and terminal prostaglandin synthases. DP1-2 receptors bind to PGD2). Several prostaglandin E synthases have been identified. and TP.Prostaglandins are produced following the sequential oxidation of AA. The diversity of receptors means that prostaglandins act on an array of cells and have a wide variety of effects such as: • • • • • • • • cause constriction or dilation in vascular smooth muscle cells cause aggregation or disaggregation of platelets sensitize spinal neurons to pain induce labour decrease intraocular pressure regulate inflammatory mediation regulate calcium movement control hormone regulation . while COX-1 and COX-2 are both located in the blood vessels.. [edit] Other terminal prostaglandin synthases Terminal prostaglandin synthases have been identified that are responsible for the formation of other prostaglandins. EP1-4. However. To date. COX-2 produces prostaglandins through stimulation.β from PGD2 and PGF2α from PGH2 in the presence of NADPH. [edit] Prostaglandin E synthase Prostaglandin E2 (PGE2) is generated from the action of prostaglandin E synthases on prostaglandin H2 (PGH2). hematopoietic and lipocalin prostaglandin D synthases (hPGDS and lPGDS) are responsible for the formation of PGD2 from PGH2. For example. IP1-2. A third form of COX. Prostaglandins ligate a sub-family of cell surface seven-transmembrane receptors. corresponding to the receptor that ligates the corresponding prostaglandin (e. stomach and the kidneys. [edit] Function There are currently ten known prostaglandin receptors on various cell types. termed COX-3 is thought to exist in the brain and may be associated with relief of Headaches when on NSAID therapy. Similarly. FP.

prostaglandin E2 (PGE2).control cell growth acts on thermoregulatory center of hypothalamus to produce fever acts on mesangial cells in the glomerulus of the kidney to increase Glomerular filtration rate • • • Prostaglandins are potent but have a short half-life before being inactivated and excreted. they send only paracrine (locally active) or autocrine (acting on the same cell from which it is synthesized) signals. Type Receptor • • • • Function vasodilation inhibit platelet aggregation bronchodilatation bronchoconstriction GI tract smooth muscle contraction bronchodilatation GI tract smooth muscle relaxation vasodilatation ↓ gastric acid secretion ↑ gastric mucus secretion uterus contraction (when pregnant) GI tract smooth muscle contraction lipolysis inhibition ↑ autonomic neurotransmitters [8] PGI2 IP EP1 • • • • • • • • • • • EP2 PGE2 EP3 ↑ platelet response to their agonists [9] [1] and ↑ atherothrombosis in vivo [10][2] • hyperalgesia[8] Unspecified • • pyrogenic uterus contraction bronchoconstriction PGF2α FP • [edit] Role in pharmacology . prostacyclin I2 (PGI2). Therefore. [edit] Types The following is a comparison of different types of prostaglandin. and prostaglandin F2α (PGF2α).

^ "essential fatty acid (EFA)" at Dorland's Medical Dictionary 6. ISBN 3-527-29284-5.). J.jphysiol. a progesterone antagonist). PMID ISBN 0-87893-617-3. ^ Goldblatt MW (May 1935). doi:10. Watanabe K. http://www. E. Yamada T. "Prostaglandin F2alpha formation from prostaglandin H2 by prostaglandin F synthase (PGFS): crystal structure of PGFS containing bimatoprost". PMID 16994667. 5. An introduction to behavioral endocrinology (3rd ed. Takusagawa F (2004). Randy F. ^ Nelson. (2005).springerlink.pdf. Yamada T. Classics in Total Synthesis. "Properties of human seminal plasma". ^ Komoto J. Watanabe K.[11] • To treat egg binding in small birds[12] • As an ingredient in eyelash and eyebrow growth beauty products due to side effects associated with increased hair growth • [edit] References 1. Sorensen (1996). Biochemistry 43 (8): 2188–98. Wien Klin Wochenschr 14 (33): 1182– 2. with or without mifepristone. 3. "Crystal structure of human prostaglandin F synthase (AKR1C3)". Takusagawa F (2006). http://www. Sunderland.1021/bi036046x. 7. 100. a synthetic prostamide analog with ocular hypotensive activity) • To treat erectile dysfunction or in penile rehabilitation following surgery (PGE1 as alprostadil). C. ^ Von Euler US (1935). doi:10. p. 65. Woodward D. PMC 1394818. "Über die spezifische blutdrucksenkende Substanz des menschlichen Prostata. ^ Komoto J.und Samenblasensekrets" (PDF). • To prevent closure of patent ductus arteriosus in newborns with particular cyanotic heart defects (PGE1) • To prevent and treat peptic ulcers (PGE) • As a vasodilator in severe Raynaud's phenomenon or ischemia of a limb • In pulmonary hypertension • In treatment of glaucoma (as in bimatoprost ophthalmic solution. pp. Weinheim. Mass: Sinauer Associates.. Germany: VCH. .1021/bi051861t.[edit] Inhibition See also: Prostaglandin antagonist and Mechanism of action of aspirin Examples of prostaglandin antagonists are: • • • • NSAIDs (inhibit cyclooxygenase) Corticosteroids (inhibit phospholipase A2 production) COX-2 selective inhibitors or coxibs Cyclopentenone prostaglandins may play a role in inhibiting inflammation [edit] Clinical uses Synthetic prostaglandins are used: To induce childbirth (parturition) or abortion (PGE2 or PGF2. K. J Physiol 84 (2): 208–18. ^ Nicolaou. 4. Biochemistry 45 (7): 1987–96. PMID 14979715.

DVM. Athirakul K. Retrieved 2008-01-26. ISBN 0-443-07145-4. ^ LaBonde. McNeish JD. 107:603 10. Jerry. 2007. Koller BH. P. http://web. Michigan Veterinary Medical onde2. Journal of Clinical investigation. (2003). Edinburgh: Churchill Livingstone. Austin S. 2001. ^ Medscape Early Penile Rehabilitation Helps Reduce Later Intractable ED 12. FitzGerald GA. ^ a b Rang. Coggins K.pdf. Vonesch JL. Hentsch D. "Avian Reproductive and Pediatric Disorders" (PDF). Parise LK. H. [edit] External links • • • • • • • MeSH Prostaglandins • .Tilly P. Coffman TM. Fabre JE. Nguyen M.).michvma. 234.8.archive. ^ Fabre JE. ^ Gross S. Pharmacology (5th ed. Journal of Experimental Medicine. 204:311 11. MS. Archived from the original on 2008-02-27. pp.