Prostaglandin E2 and

Aspirin sensitive asthma, affecting about 10% of all asthmatics, is a nonallergic response to aspirin and other agents that inhibit cyclooxygenase-1. Mechanistically, the most likely reasons are lack of bronchoprotective prostaglandin E2 and shunting of arachidonic acid into the leukotriene pathway. 

Endothelial cells are the major source of ET-1-synthesis. ET-1 is also produced by astrocytes, neurons, hepatocytes, bronchial epithelial cells, renal epithelial and mesangial cells. Physiological stimuli of ET-1-synthesis in endothelial cells are angiotensin II, catecholamines, thrombin, growth factors, insulin, hypoxia and shear stress. Inhibitors of ET-1 synthesis are atrial natriuretic peptide, prostaglandin E2 and prostacyclin. ET-2 is mainly synthesized in kidney, intestine, myocardium and placenta and ET-3 is predominantely produced by neurons, astrocytes and renal epithelial cells. 

Hammarstrom, S., Hamberg, M., Samuelsson, B., Duell, E.A., Stawiski, M. and Voorhees, J.J. (1975). Increased concentrations of non-esterified arachidonic acid, 12L-hydroxy-5,8,10,14-eicosatetraenoic acid, prostaglandin E2 and prostaglandin F2 in epidermis of psoriasis. Proc. Natl Acad. Sci. USA 72, 5130-5134. 

Minghetti,L., Greco,A., Cardone, F., Puopolo,M.,Ladogana, A. and Almonti, S. Increased brain synthesis of prostaglandin E2 and F2-isoprostane in human and experimental transmissible spongiform encephalopathies.. Neuropathol. Exp. Neurol. 59 866-871, 2000. 

I to angiotensin II, a potent vasoconstrictor and stimulator of aldosterone secretion. ACE inhibitors also block the degradation of bradykinin and stimulate the synthesis of other vasodilating substances including prostaglandin E2 and prostacyclin. The fact that ACE inhibitors lower BP in patients with normal plasma renin activity suggests that bradykinin and perhaps tissue production of ACE are important in hypertension. 

The enzyme prostaglandin H2 synthase-1 (PGHS-1) manufactures prostaglandin H2, which is converted to prostaglandin E2 and causes fever and inflammation. PGHS-1 contains two protein subunits with long channels. 

In mast cells, histamine release induced by IgE or A23187 was also inhibited by feverfew extract [48] which also reduced spasmolytic activity of smooth muscle induced by acetylcholine, 5HT, histamine, prostaglandin E2 and bradykinin [20]. 

Furosemide Furosemide stimulates renal synthesis of prostaglandin E2 and may increase the incidence of patent ductus arteriosus when given in the first few weeks of life, to premature infants with respiratory-distress syndrome. 

Smith AP, Cuthbert MF. The response of normal and asthmatic subjects to prostaglandins E2 and F2alpha by different routes, and their significance in asthma. Adv Prostaglandin Thromboxane Res 1976 1 449-59. 

Faust TW, Redfern JS, Podolsky I, Lee E, Grundy SM, Feldman M. Effects of aspirin on gastric mucosal prostaglandin E2 and F2 alpha content and on gastric mucosal injury in humans receiving fish oil or olive oil. Gastroenterology 1990 98(3) 586-91. 

Bickel, M., and G.L. Kauffman, Jr. 1981. Gastric gel mucus thickness Effect of distention, 16,16-dimethyl prostaglandin e2, and carbenoxolone. Gastroenterology 80 770. 

Smooth muscles and vascular smooth muscles Prostaglandins E2 and I2 cause arteriolar dilation in the systemic and pulmonary vascular beds. Prostaglandins and E2, as well as thromboxane B2, constrict the human umbilical cord. Leukotrienes C4 and D4, which release prostaglandin E, decrease peripheral vascular resistance. 

Cardiovascular system Prostaglandins E2 and F2(x have positive isotropic effects and generally elicit increases in the cardiac output. 

Krueger JM, Kapas L, Opp MR, Obal F Jr. Prostaglandins E2 and D2 have little effect on rabbit sleep. Physiol Behav 1992 51 481-485. 

Gold alters the morphology and functional capabilities of human macrophages—possibly its major mode of action. As a result, monocyte chemotactic factor-1, interleukin-8, interleukin-IB production, and vascular endothelial growth factor are all inhibited. Intramuscular gold compounds also alter lysosomal enzyme activity, reduce histamine release from mast cells, inactivate the first component of complement, and suppress the phagocytic activities of polymorphonuclear leukocytes. Auranofin also inhibits release of prostaglandin E2 and leukotriene B4. 

Cyclooxygenase-2, Prostaglandin E2, and Microglial Activation in Prion Diseases Luisa Minghetti and Maurizio Pocchiari... 

In addition to inflammation, another potential role for natural COX and LOX dual inhibitors is in the prevention and treatment of cancers [80], Over expression of COX-2 has been demonstrated in various different human malignancies. COX-2 inhibitors have also been shown to be efficacious in the treatment of animal models of skin, breast and bladder tumors. While the mechanism of action remains to be completely defined, the over expression of COX-2, in excess of production of prostaglandin E2 and 5-hydroxyeicosatetraenoic acid (5-HETE) have been shown to inhibit apoptosis and increase the invasiveness of tumerogenic cell types [81,82]. It is probable that the enhanced production of PGE2 and 5-HETE promotes cellular proliferation, and consequently, increases angiogenesis [83]. 

Studies with ovarian cells have also shown that extracellular calcium is required to give maximum steroidogenesis [29]. The calcium channel blockers, verapamil or diltiazem also suppressed LH-stimulated progesterone production. The calcium ionophore A23187 significantly enhanced the stimulatory effects of LH. Recently it was shown that FSH, prostaglandin E2 and F2 have distinct effects on steady state calcium exchange in ovarian cells [30]. 

Dysmenorrhoea is painful or difficult menstruation with severe abdominal cramps. Symptoms are related to the actions of prostaglandins E2 and F2Q , which are released in the uterus during menstruation. Analgesics, for example aspirin, can be used to treat pain suppression of ovulation using combined oral contraceptives is effective in minimizing these symptoms. 

---