e Cosa Noids

7/30/2019 e Cosa Noids

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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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17

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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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