Local mediators

In summary, the lysophospholipids are local mediators that regulate development, tissue regeneration and homoeostasis, but also play a role in inflammation, arteriosclerosis and cancer. 

Among the local mediators directly produced by endothelium, NO and PGI emerge as two principal regulators of vascular tone and platelet aggregation. Both are sensitive to estrogenic stimuli, and, as mentioned in a previous section, their role is crucial in atherogenesis. How their production is modulated by SERMs is, consequently, an important test of vascular protection. 

In the vasculature release of local mediators such as endothelin, prostacyclin and nitric oxide can only affect the local vasotone (at the site of release) or regulate downstream constriction or dilation. Besides this, upstream regula-... 

Serhan C. N. (2005b). Novel m-3-derived local mediators in anti-inflammation and resolution. Pharmacol. Ther. 105 7-21. 

Schomig, A., Dart, A.M., Dietz, R., Mayer, E., and Kubler, W. 1984. Release of endogenous catecholamines in the ischemic myocardium of the rat. Part A Locally mediated release. Circ. Res. 55 689-701. 

Neurotransmission in the autonomic nervous system is an example of the more general process of chemical signaling between cells. In addition to neurotransmission, other types of chemical signaling are the release of local mediators and the secretion of hormones. 

Most cells in the body secrete chemicals that act locally, that is, they act on cells in their immediate environment. These chemical signals are rapidly destroyed or removed thus, they do not enter the blood and are not distributed throughout the body. Histamine (see p. 420) and prostaglandins (see p. 419) are examples of local mediators. 

All eicosanoids are very potent compounds present in low concentration in cells. They are local mediators, meaning that they perform their function in the environment in which they are synthesized. This distinguishes them from hormones, which are first synthesized and then transported in the bloodstream to their site of action. Eicosanoids are not stored in cells rather, they are synthesized from arachidonic acid in response to an external stimulus. 

Recently Liu and Weller [84] have reviewed the arachidonic acid metabolism in filarial parasites and other helminths. Arachidonic acid (AA) is a 20 carbon polyunsaturated fatty acid derived from dietary fatty acids. In human tissues, AA is usually present in the esterified form such as glycerolipids, phospholipids and neutral lipids. The free AA, released by phospholipases, undergoes various enzymatic oxygenations to form local mediators such as prostaglandins and leukotrienes, which are collectively known as eicosanoids (Chart 9). These eicosanoids are associated with platelet aggregation, vasodilation, leukocyte inflammatory and immune functions and cellular adhesion [85]. 

Glucocorticoids interfere with macrophage action, decrease capillary permeability, and decrease the activity of local mediators (see Figure). 

PKA diversity lies in both its R and C subunits. Molecular cloning has revealed a and [3 isoforms of both the classically described PKA regulatory subunits (RI and RII), as well as three C subunit isoforms Ca, Cfi, and Cy. The R subunits exhibit different binding affinities for cyclic AMP giving rise to PKA holoenzymes with different thresholds for activation. In addition to differential expression of R and C isoforms in various cells and tissues, PKA function is modulated by subcellular localization mediated by A-kinase-anchoring proteins (AKAPs). 

Paracrine hormones, also termed local mediators, peptide hormones involved in biochemical communications which are directed to surrounding cells by diffusion. 

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