Prostaglandins Eicosanoids

The pharmacological effects of the prostaglandins and TXAj comprise many different activities—in fact too many. The lack of specificity of their activities implies a number of side effects which preclude the clinical application of several highly active natural prostaglandins, necessitating the development of selective synthetic compounds. The following effects of prostaglandins/eicosanoids are known and are summarized in table 8.3. 

Vol. 5 From the Contents Osmoregulation - Chemoreception -Temperature - Spectroscopy - Metalloproteins Prostaglandins (Eicosanoids) -Maternal-Fetal Relationships (1989)... 

Allergic Seasonal or Perennial Rhinoconjunctivitis. Histamine can cause all pathologic features of allergic rhinitis (35—37), with the exception of late-phase inflammatory reactions. Pmritus is caused by stimulation of receptors on sensory nerve endings prostaglandins (qv) may also contribute. Sneering, like pmritus, is an H -mediated neural reflex and can also be mediated by eicosanoids. Mucosal edema, which manifests as nasal... 

Detailed accounts of the biosynthesis of the prostanoids have been pubUshed (14—17). Under normal circumstances arachidonic acid (AA) is the most abundant C-20 fatty acid m vivo (18—21) which accounts for the predominance of the prostanoids containing two double bonds eg, PGE2 (see Fig. 1). Prostanoids of the one and three series are biosynthesized from dihomo-S-linolenic and eicosapentaenoic acids, respectively. Concentrations ia human tissue of the one-series precursor, dihomo-S-linolenic acid, are about one-fourth those of AA (22) and the presence of PGE has been noted ia a variety of tissues (23). The biosynthesis of the two-series prostaglandins from AA is shown ia Eigure 1. These reactions make up a portion of what is known as the arachidonic acid cascade. Other Hpid products of the cascade iaclude the leukotrienes, lipoxins, and the hydroxyeicosatetraenoic acids (HETEs). Collectively, these substances are termed eicosanoids. 

Prostaglandins, together with related compounds called thromboxanes and leukotrienes, make up a class of compounds called eicosanoids because they are derived biologically7 from 5,8,11,14-eicosatetraenoic acid, or arachidonic... 

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. 

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 These compounds, derived from eicosa- (20-carbon) polyenoic fatty acids, comprise the prostanoids, leukotrienes (LTs), and lipoxins (LXs). Prostanoids include prostaglandins (PGs), prostacyclins (PGIs), and thromboxanes (TXs). 

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 23-5. The three groups of eicosanoids and their biosynthetic origins. (PG, prostaglandin PGI, prostacyclin TX, thromboxane LT, leukotriene LX, lipoxin , cyclooxygenase pathway , lipoxygenase pathway.) The subscript denotes the total number of double bonds in the molecule and the series to which the compound...

Histamine Serotonin Platelet-activating factor (PAF) Eicosanoids (various prostaglandins and leukotrienes) C3a, C4a, and C5a from the complement system Bradykinin and fibrin split products from the coagulation system... 

Wolfe, CS (1982) Eicosanoids prostaglandins, thromboxanes, leukotrienes and other derivatives of carbon-20 unsaturated fatty acids. J. Neurochem. 38 1-9. 

Halliwell, B. and Gutteridge, J.M.C. (1989). Eicosanoids prostaglandins and leucotrienes. In Free Radicals in Biology and Medicine pp. 401-403. Clarendon Press, Oxford. 

Foegh, M.L. and Ramwell, P.W., The eicosanoids prostaglandins, thromboxanes, leukotrienes and related compounds, in Basic and Clinical Pharmacology, 8th ed., Katzung, B.G., Ed., Lange Medical Books/McGraw-Hill, New York, 2001, chap. 18. 

Lipids have multiple roles in cells. Recent discoveries show that the same lipid may have both structural and regulatory roles in the cell. For example, while arachidonic acid (20 4co6) is a major constituent of brain inositides and PtdEtn, the free acid is also a precursor of a number of important bio messengers, the eicosanoids, such as prostaglandins, prostacyclins, leukotrienes and thromboxanes... 

---