Professional Documents
Culture Documents
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 fatty acids with twenty carbons. Paracrine or autocrine messengers molecules
Short half-lives (10 secs 5 mins) so that functions are usually limited to actions on nearby cells.
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 hormones in that they are produced in very small amounts in almost all tissues rather than in specialized glands.
They also act locally rather than after transport in the 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 metabolized to inactive products at their site of synthesis. Their biologic actions are mediated by plasma and nuclear membrane receptors, which are different in different organ systems.
Inflammatory Biomolecules
Signal Molecules
Histamine Eicosanoids
Prostaglandins Thromboxanes Leukotrienes
Bradykinins Cytokines
Interferons Interleukins Chemotaxins
Made in almost all tissues Very short half-life Act locally on neighbors Not usually stored up 20-carbon backbones Made from arachidonic acid
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)
Plasma membrane
Stimulus
Membrane-bound phospholipids
Arachidonic acid
Tromboxanes induce constriction of blood vessels and platelet aggregation (blood clotting)
Prostaglandins stimulate inflammation,regulate blood flow, control ion transport and modulate synaptic transmission.
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.
Thromboxane A2 stimulates constriction of blood vessels and platelet aggregation Prostacyclin dilates blood vessels and inhibits platelet aggregation
Prostaglandins mediate aspects of inflammatory response Stimulation of smooth muscle by PGE2
2. Inflammatory response
3. Reproductive system
4. Gastrointestinal tract
17.2 Fatty Acids
Prostaglandins inhibit gastric secretion Prostaglandins increase secretion of protective mucus Inhibition of hormone-sensitive lipases Prostaglandins dilate renal blood vessels Results in increased water and electrolyte excretion Leukotrienes promote the constriction of bronchi Prostaglandins promote bronchodilation
5. Kidneys
6. Respiratory tract