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Eicosaniods
Derived from 20-crabon polyunsaturated fatty acids.
Prostaglandins (PG), and the related compounds thromboxanes
(TX) and leukotrienes (LT), are collectively known as
eicosanoids to reflect their origin from polyunsaturated fattyacids with twenty carbons.
Paracrine or autocrine messengers molecules
Short half-lives (10 secs5 mins) so that functions are usually
limited to actions on nearby cells.
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Bind to specific cell surface G-protein coupled receptors,
and generally increase cAMP levels. May also bind to
nuclear receptors and alter gene transcription.
They are extremely potent compounds that elicit a wide
range of responses, both physiologic and pathologic.
Although they have been compared to hormones in terms
of their actions, eicosanoids differ from the true hormonesin that they are produced in very small amounts in almost
all tissues rather than in specialized glands.
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They also act locally rather than after transport inthe blood to distant sites, as occurs with true
hormones such as insulin.
Eicosanoids are not stored, and they have an
extremely short half-life, being rapidly metabolizedto inactive products at their site of synthesis.
Their biologic actions are mediated by plasma and
nuclear membrane receptors, which are different indifferent organ systems.
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Inflammatory Biomolecules
Signal Molecules Histamine
Eicosanoids
Prostaglandins
Thromboxanes
Leukotrienes
Bradykinins
Cytokines
Interferons
Interleukins
Chemotaxins
Other minor molecules...
Made in almost all tissues
Very short half-life
Act locally on neighbors
Not usually stored up
20-carbon backbones
Made from arachidonic acid
E.A. DENNIS 2010
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Major Classes of Eicosanoids
Prostaglandins
Thromboxanes
Prostacyclins
Leukotrienes
HETES
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Classes of eicosanoids
1. Prostanoids - have a ring structure
a. Prostaglandins (PGs)
b. Prostacyclins (PGIs) c. Thromboxanes (TXs)
2. Linear eicosanoids - no ring structure a. Leukotrienes (LTs)
b. Lipoxins (LXs)
c. Hydroxyeicosatetraenoic acids (HETEs)
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Arachidonic acid
Plasmamembrane Arachidonate is derived from
membrane phospholipids
Membrane-boundphospholipids
Stimulus
Tromboxanes induce constriction
of blood vessels and platelet
aggregation (blood clotting)
Prostaglandins stimulateinflammation,regulate bloodflow, control ion transport and
modulate synaptic transmission.
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Prostanoid biosynthesis
Eicosanoids are not stored by cells, but rather are synthesized
and released rapidly (5-60 s) in response to extracellular
hormonal stimuli.
Prostanoid formation occurs in three stages:
(a)mobilization of free arachidonic acid from membrane
phospholipids;
(b)conversion of arachidonate (or 2-AG) to the prostaglandin
endoperoxide PGH2
(c) cell-specific conversion of PGH2 to one of the major
prostanoids.
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FattyAcids
Thromboxane and Leukotriene
Structure
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Biological Processes Regulated by
Eicosanoids
1. Blood clotting
Thromboxane A2 stimulates constriction ofblood vessels and platelet aggregation
Prostacyclin dilates blood vessels and inhibitsplatelet aggregation
2. Inflammatory response
Prostaglandins mediate aspects of
inflammatory response
3. Reproductive system
Stimulation of smooth muscle by PGE2
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FattyAcids
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4. Gastrointestinal tract
Prostaglandins inhibit gastric secretion
Prostaglandins increase secretion of protective mucus Inhibition of hormone-sensitive lipases
5. Kidneys
Prostaglandins dilate renal blood vessels
Results in increased water and electrolyte excretion
6. Respiratory tract
Leukotrienes promote the constriction of bronchi
Prostaglandins promote bronchodilation
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FattyAcids
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