Eicosanoids physiology

Stanley-Samuelson, D. W., Comparative eicosanoid physiology in invertebrate animals, Am. J. Physiol., 260, R849, 1991. 

Among vertebrate species, the neuro-endocrine-immime system is responsible for many complex, inter-related physiological processes including neuronal, homeostatic, reproductive and immune functions. There are four main types of hormone polypeptides, eicosanoids, steroids and thyroid hormones. Reflecting the inter-dependency of the neiiro-endocrine and immune systems, hormones, neuropeptides and other neiirotransmitters are known to be produced by some immune cells and play a role in the regulation of the immune system, while endocrine and nervous tissues express receptors for many substances produced by the immune system. The major focus of interest in endocrine disruption has... 

Eicosanoids and terpenoids are still other classes of lipids. Eicosanoids, of which prostaglandins are the most abundant kind, are derived biosynthetically from arachidonic acid, are found in all body tissues, and have a wide range of physiological activity. Terpenoids are often isolated from the essential oils of plants, have an immense diversity of structure, and are produced biosynthetically from the five-carbon precursor isopentenyl diphosphate (IPP). lsopentenyl diphosphate is itself biosynthesized from 3 equivalents of acetate in the mevalonate pathway. 

Steroids are plant and animal lipids with a characteristic tetracyclic carbon skeleton. Like the eicosanoids, steroids occur widely in body tissues and have a large variety of physiological activities. Steroids are closely related to terpenoids and arise biosynthetically from the triterpene lanosterol. Lanosterol, in turn, arises from cationic cyclization of the acyclic hydrocarbon squalene. 

Prostaglandins are a group of lipid autacoids known as eicosanoids. They are produced from membrane phospholipids and found in almost every tissue and body fluid. They are involved in a number of physiological processes including inflammation, smooth muscle tone and gastrointestinal secretion. In the central nervous system they have been reported to produce both excitation and inhibition of neuronal activity. 

Eicosanoids are formed from 20-carbon polyunsaturated fatty acids and make up an important group of physiologically and pharmacologically active compounds known as prostaglandins, thromboxanes, leukotrienes, and lipoxins. 

FIGURE 57-2. Eicosanoid synthesis pathway. Cyclooxygenase is inhibited by nonsteroidal anti-inflammatory drugs and aspirin. (From Widmaier EP, Raff H, Strang KT, et al, (eds.) Vander, Sherman, Luciano s Human Physiology The Mechanisms of Body Function. 9th ed. New York McGraw-Hill 2004, Figure 5-11.)... 

Like nitric oxide, the discovery of the eicosanoid signalling molecules was a significant event in twentieth century physiology, due largely to research led by Sir John Vane (Nobel Prize 1982). The diverse actions of the eicosanoids include roles in muscle contraction, blood coagulation, salt and fluid homeostasis, inflammatory responses and pain sensitivity. 

Four principal mechanisms have been cited to explain the diverse physiological mechanisms of ginger. Broadly, these are (1) eicosanoid inhibition, (2) serotonin antagonism, (3) substance P release, and (4) Ca2-i-/ATPase activity. 

The eicosanoids have a broad spectrum of physiological activities and these are elicited at very low concentrations, 10 M or less. They mediate the inflammatory response, produce pain and fever, regulate blood pressure, initiate blood clotting, induce labor, and regulate the sleep/wake cycle. 

Eicosanoids include prostaglandins, prostacyclins, thromboxanes, and leukotrienes. Molecules in these classes have a spectrum of physiological activities. 

Eicosanoids are involved in control of a number of physiological processes that are essential to life. Some information on each role is provided below but further detail can be found in other chapters clotting of blood (Chapters 17 and 22) menstruation and parturition (Chapter 19) secretion of protons in the stomach (Chapter 4) pain and fever (Chapter 18). 

Figure 20.3 Essential fatty acids in the diet, production of physiological essential acids and their roles in the cell cycle. Essential fatty adds in the diet are mainly linoleic and a-linolenic but they are converted by desaturation and elongation reactions to the essential acids that are used in phospholipid formation and synthesis of eicosanoids. (For details of the elongation and desaturation reactions and eicosanoid formation, see Chapter 11.).

The eicosanoids are a group of signaling substances that arise from the C-20 fatty acid arachidonic add and therefore usually contain 20 C atoms (Greek eicosa = 20). As mediators, they influence a large number of physiological processes (see below). Eicosanoid metabolism is therefore an important drug target. As short-lived substances, eicosanoids only act in the vicinity of their site of synthesis (paracrine effect see p.372). 

COX-1 is constitutively expressed in many cells of the body and responsible mainly for the production of eicosanoids serving normal physiological functions. One important physiological role is the protection of the gastric mucosa. Inhibition of COX-1 therefore often brings pain relief together with gastrointestinal side-effects. 

Physiological and Pathophysiological Effects of Eicosanoids 5.6.1 Neurotrophic Effects... 

Other Pathologies. Because of their many varied physiologic effects, the eicosanoids are involved in a number of other pathologic conditions. Prostaglandins have been implicated in cardiovascular disorders (hypertension), neoplasms (colon cancer), respiratory dysfunction (asthma), neurologic disorders (multiple... 

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