Arachidonic acid metabolite

The actions of prostaglandins on isolated pulmonary blood vessels were reviewed by Piper and Vane (1979). Usually, E-type PG relax pulmonary vascular smooth muscle but there is some species variation in the reaction of intrapulmonary blood vessels (Palmer et al. 1973, Kadowitz et al. 1975). The intrapulmonary vessels will be exposed to the prostaglandins released in the lung by agents such as bradykinin, slow-reacting substance of anaphylaxis or histamine. 

PGE2 levels in the circulation have been detected by radioimmunoassay in amounts that could have a biological importance. However, on the basis of measurements of the major urinary and circulating metabolites, it was shown that the true levels are much smaller and in the range of a few picograms 

An infusion of bradykinin into isolated lungs of the guinea pig caused release of PGp2a (Piper and Vane 1971). 

Endothelial cells are the most active producers of prostaglandin I2 (Weksler et al. 1977, MacIntyre et al. 1978), the production persisting even after numerous subcultures in vitro (Christofinis et al. 1979). The biosynthesis of PGI2 is inhibited by 15-HPETE and other fatty acid hydroperoxides (Gryg-LEWSKi et al. 1976). 

20-Hydroxyeicosatetraenoic acid (20-HETE) is produced in human lungs and is a potent cyclooxygenase-dependent dilator of isolated pulmonary arteries (Birks et al. 1997). Small pulmonary arteries of New Zealand White rabbits express cP450 4A proteins and vascular smooth muscle cells derived from these arteries synthesise 20-HETE (Zhu et al. 1998). 

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Type I allergic reactions are inappropriate immune responses to an allergen with preferential synthesis of immunoglobulin E (IgE), a special antibody class, which binds to mast cells and basophilic granulocytes via Fee receptors. Binding of the allergen to the cell-bound IgE initiates the rapid release of allergic mediators, most prominently histamine, and the de novo synthesis of arachidonic acid metabolites and cytokines, which are responsible for the clinical symptoms. 

Tomita Y, Maeda K, Tagami H (1992) Melanocyte-stimulation properties of arachidonic acid metabolites, possible role of post-inflammatory. Cell Res 5 357-361... 

Palytoxin is hemolytic (4) and is an extremely potent toxin (7). We have shown that in rat liver cells palytoxin stimulates de-esterification of cellular lipids to liberate arachidonic acid (5). These rat liver cells metabolize this increased arachidonic acid via the cyclooxygenase pathway to produce prostaglandin (PG) I2 and lesser amounts of PGE2 and PGp2. Palytoxin acts on many cells in culture to stimulate the production of cyclooxygenase metabolites (Table I). Clearly, the myriad pharmacological effects of the arachidonic acid metabolites must be considered in any explanation of the many clinical manifestations of palytoxin s toxicity. 

Schlondorff, D. and Ardaillon, R. (1986). Prostaglandins and other arachidonic acid metabolites in the kidney. Kidney Int. 29, 108-119. 

Aspirin is maximally effective as an antithrombotic agent at the comparatively low dose of 81 to 325 mg per day. (The antipyretic dose of aspirin in adults is 325 to 650 mg every 4 h.) Higher doses of aspirin are actually contraindicated in patients prone to thromboembolism. At higher doses, aspirin also reduces synthesis of prostacyclin, another arachidonic acid metabolite. Prostacyclin normally inhibits platelet aggregation. The prophylactic administration of low-dose aspirin has been shown to increase survival following myocardial infarction, decrease incidence of stroke, and assist in maintenance of patency of coronary bypass grafts. 

Fig. 2. Arachidonic acid metabolites identified in Aplysia californica nervous tissue...

Arachidonic acid metabolite DMQPH TCPO 500 amol 78... 

TNF-a is considered the primary mediator of sepsis, and concentrations are elevated early in the inflammatory response during sepsis, and there is a correlation with severity of sepsis. TNF-a release leads to activation of other cytokines associated with cellular damage and it stimulates release of arachidonic acid metabolites that contribute to endothelial cell damage. IL-6 is a more consistent predictor of sepsis as it remains elevated for longer periods of time than does TNF-a. 

Assaad, A., Trotz, M., Moore, D., Nold, J, Corcoran, K., Hurt, H., Keeler, J., Phillips, K., and Said, S.I. 1990. Arachidonic acid metabolites as early markers of phosgene-induced acute lung injury and pulmonary edema. World Conference on Lung Health. Boston, MA. May 20-24. Am. Rev. Respir. Dis. 141 A420. 

Schwartz-Bloom RD, CookTA, Yu X. (1996). Inhibition of GABA-gated chloride channels in brain by the arachidonic acid metabolite, thromboxane A2. Neuropharmacology. 35(9-10) 1347-53. 

The biological actions of the cysteinyl leukotrienes are mediated via stimulation of CysLTi receptors. Montelukast and zafirlukast are competitive antagonists of these receptors. In contrast, zileuton suppresses synthesis of the leukotrienes by inhibiting 5-lipoxygenase, a key enzyme in the bioconversion of arachidonic acid to the leukotrienes. Zileuton also blocks the production of leukotriene B4, another arachidonic acid metabolite with proinfiammatory activity. The CysLTi-receptor antagonists alter neither the production nor the actions of leukotriene B4. 

Another important aspect of the inflammatory cascade is arachidonic acid metabolism, leading to the synthesis of the proinflammatory prostaglandins and leukotrienes. Through the formation of Upocortin, an inhibitor of phospholipase A2, glucocorticoids depress the release of arachidonic acid from phospholipids and hence the production of arachidonic acid metabolites. 

NT259 Ringdahl, B. E., G. K. Johnson, R. B. Ali, and C. C. Organ. Effect of nicotine on arachidonic acid metabolites and epithelial parameters in rat oral mucosa. J Oral Pathol Med 1997 26(1) 40-45. 

Molina, V., M. L. Arruzazabala M. L, D. Carbajal, and R. Mas. D-003, a potential antithrombotic compound isolated from sugar cane wax with effects on arachidonic acid metabolites. Prostaglandins Leuko Essent Fatty Acids 2002 67(1) 19-24. 

Mechanism of Action A salicylic acid derivative that locally inhibits arachidonic acid metabolite production, which is increased in patients with chronic inflammatory bowel disease. Therapeutic Effect Blocks prostaglandin production and diminishes inflammation in the colon. 

Gordon T, Thompson JE, Sheppard D. 1988. Arachidonic acid metabolites do not mediate toluene diisocyanate-induced airway hyperresponsiveness in guinea pigs. Prostaglandins 35(5) 699-706. 

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