Chapter VI Eicosanoids (Prostaglandis)

LIPIDS AS SIGNALS : Phosphatidyl Inositols and its phosphorylated derivatives act to regulate cell structure and metabolism. Eicosanoids are paracrine hormones derived from arachidonic acid-containing membrane phospholipids. They are involved in reproductive function, inflammation, fever, pain, blood clot formation, blood pressure regulation, gastric acid secretion, and other biological processes.

Overview Eicosanoids are a large group of autocoids with potent effects on virtually every tissue in the body these agents are derived from metabolism of 20-carbon, unsaturated fatty acids (eicosanoic acids).

The eicosanoids include: the prostaglandins thromboxanes leukotrienes hydroperoxyeicosatetraenoic acids (HPETEs) hydroxyeicosatetraenoic acids (HETEs).

Prostaglandin: One of a number of hormone-like substances that participate in a wide range of body functions such as the contraction and relaxation of smooth muscle, the dilation and constriction of blood vessels, control of blood pressure, and modulation of inflammation. Prostaglandins are derived from a chemical called arachidonic acid. The prostaglandins are a group of physiologically active lipid compounds having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals

Biosynthesis Arachidonic acid, the most common precursor of the eicosanoids, is formed by two pathways: Phospholipase A2-mediated production from membrane phospholipids; this pathway is inhibited by glucocorticoids. Phospholipase C.

Eicosanoids are synthesized by two pathways: The prostaglandin H synthase (COX, cyclooxygenase) pathway produces: thromboxane the primary prostaglandins prostaglandin E, or PGE prostaglandin F, or PGF prostaglandin D, or PGD) prostacyclin (PGI2)

PGI PGE PGF Type Function vasodilation inhibit platelet aggregation bronchodilation PGE bronchoconstriction GI tract smooth muscle contraction GI tract smooth muscle relaxation  gastric acid secretion gastric mucus secretion uterus contraction (when pregnant) lipolysis inhibition  autonomic neurotransmitters [8] platelet response to their agonists [ and atherothrombosis in vivo  PGF uterus contraction

Gastrointestinal tract PGE2 and PGF2a increase the rate of longitudinal contraction in the gut and decrease transit time. The leukotrienes are potent stimulators of gastrointestinal smooth muscle. PGE2 and PGI2 inhibit acid and pepsinogen secretion in the stomach. Prostaglandins increase mucus, water, and electrolyte secretion in the stomach and the intestine.

Blood TXA2 PGI2 and PGE2 PGEs 5-HPETE PGI2 and PGD is a potent inducer of platelet aggregation. PGI2 and PGE2 inhibit platelet aggregation. PGEs induce erythropoiesis by stimulating the renal release of erythropoietin. 5-HPETE stimulates release of histamine PGI2 and PGD inhibit histamine release.

Prostaglandin E1 (PGE1) 7-[(1R,3R)-3-hydroxy-2-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-5-oxocyclopentyl]heptanoic acid The synthetic variant is known pharmaceutically as alprostadil.[ It is a drug used in the continuous treatment of erectile dysfunction. hasvasodilatory properties.  Misoprostol is another synthetic prostaglandin E1 analog used to prevent gastric ulcers when taken on a continuous basis, to treat missed miscarriage, to induce labor, and to induce abortion.

Alprostadil Indications and Usage Palliative therapy to maintain patency of ductus arteriosus temporarily, until surgery can be performed, in newborns who have congenital heart defects (eg, pulmonary stenosis, tricuspid atresia) and who depend on patent ductus for survival. Treatment of erectile dysfunction caused by neurogenic, vasculogenic, psychogenic, or mixed etiology. Intracavernosal alprostadil may be useful adjunct to other diagnostic tests in the diagnosis of erectile dysfunction.