Eicosanoids paracrine effects

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). 

Adipocytes have an important secretory function. Numerous factors (collectively termed adipokines or adipocytokines), mostly peptides but also eicosanoids are produced by preadipocytes and mature adipocytes (Table 9.3). Some of these factors act in an autocrine or paracrine fashion to regulate adipogenesis, that is differentiation and maturation of adipocytes themselves, whilst others, notably, leptin, adiponectin and some cytokines act in truly endocrine way, having effects on the brain, endothelial cells, liver and skeletal muscle. Disturbance in secretion from adipocytes is associated with eating disorders and metabolic syndrome. 

Effects. Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis, both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action). Many of their effects are mediated by the second messengers cAMP and cGMP. 

The eicosanoids—prostaglandins (PGs), thromboxanes (TXs), prostacyclins (PGIs), and leukotrienes (LTs)—are derived from essential fatty acids and act similarly to hormones (Chapter 30). However, they are synthesized in almost all tissues (unlike hormones, which are synthesized in selected tissues) and are not stored to any significant extent their physiological effects on tissues occur near sites of synthesis rather than at a distance. They function as paracrine messengers and are sometimes referred to as autacoids. 

Eicosanoids are paracrine hormones, substances that act only on cells near the point of hormone synthesis instead of being transported in the blood to act on cells in other tissues or organs. These fatty acid derivatives have a variety of dramatic effects on vertebrate tissues. They are known to be involved in reproductive function in the inflammation, fever, and pain associated with injury or disease in the formation of blood clots and the regulation of blood pressure in gastric acid secretion and in a variety of other processes important in human health or disease. 

Some of the biologic effects of certain eicosanoids occur as a result of a paracrine or autocrine action. One paracrine action is the contraction of vascular smooth muscle cells caused by TXA2 released from circulating platelets (vasoconstriction). An autocrine action of eicosanoids is exemplified by platelet aggregation induced by TXA2 produced by the platelets themselves. 

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