Prostaglandin

The prostaglandins (PG) 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. They are derived enzymatically from fatty acids.

1. PROSTAGLANDIN By: Nimmy.A.Shibu Group:4

2. INTRODUCTION The prostaglandins (PG) are a group of physiologically active lipid compounds having diverse hormone-like effects in animals. They are derived enzymatically from fatty acids. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring. They are a subclass of eicosanoids and of the prostanoid class of fatty acid derivatives. they are not secreted from a gland, but rather are created at the time they are needed directly where the problem exists.

3. TYPES OF PROSTAGLANDINS Structures of the more common prostaglandins A, E, and F are structurally related to prosranoic acid. Specific prostaglandins are named with a letter (which indicates the type of ring structure) followed by a number (which indicates the number of double bonds in the hydrocarbon structure). For example, prostaglandin E1 is abbreviated PGE1 or PGE1, and prostaglandin I2 is abbreviated PGI2 or PGI2.

4. PROSTCYCLINE- PGI2

5. PROSTAGLANDIN E2 PGE2 contains a carboxyl group, a beta- hydroxy -ketone ring, a secondary alkylic alcohol and two carbon-carbon double bonds.

6. PROSTAGLANDIN A2 A series are alpha and beta- unsarurated ketones.

7. PROSTAGLANDIN F2

8. PROSTANOIC ACID

9. FUNCTIONS cause constriction or dilation in vascular smooth muscle cells cause aggregation or disaggregation of platelets sensitize spinal neurons to pain induce labor decrease intraocular pressure regulate inflammation regulate calcium movement regulate hormones control cell growth acts on thermoregulatory center of hypothalamus to produce fever

10. BIOSYNTHESIS Synthesized aerobically from polyunsaturated fatty acids. Multienzyme comples called Prostaglandin H Synthase (PGHS). PGHS is present as two component– Cyclo-oxygenasesystem and peroxidase system. PGHS is present as two isozymes PGHS1 & PGHS2 . Phospholipase A2 released from cell membrane hydrolysis phospholipids into lysophospholipids and arachidonic acid. Arachidonic acid converted to PG by oxidative cyclization with cyclo-oxygenase of PGHS. This system forms the first unstable cyclic endoperoxide PG-G2. PG-G2 is converted to PG-H2 by glutathionine dependent peroxidase component of PGHS system. PG-H2 is the precursor of Prostanoids .

11. PHYSIOLOGICAL EFFECTS 1. Inflammation: -PGs are natural mediators of inflammation. -PGE2 & PGE1 induce signs of inflammation, edness , heat, swelling, edema. 2. Pain & Fever: -PGE2 can enhance the intensity & duration of pain caused by bradykinin & histamin . 3.Reproduction: -PGE2 & PGF2 have been used to induce parturition as well as terminate pregnancy. -PGE series of PG play role male infertility.

12. 4. Peptic Ulcers: - synthetic PGs have been useful in inhibiting gastric secretions in patients with gastric ulcers. 5. Regulation of Blood Pressure: -PGE, PGA & PGI2 being vasodilators lower the systemic arterial pressure , increase local blood flow . - help in treating hypertension. 6.PGI2 inhibit platelet aggregation. 7. PGE2 & TXA2 promote clotting process.

13. INHIBITORS NSAIDs--inhibit cyclooxygenase: Eg : aspirin, indomethacin, phenylbutazone . Corticosteroids--inhibit phospholipase A2 production: Eg : hydrocortisone, prednisone, beta- mathasone . COX-2 selective inhibitors or coxibs : Eg : anexins . Cyclopentenone prostaglandins may play a role in inhibiting inflammation .

14. CATABOLISM The most important dietary precursor of prostaglandins is linoleic acid, an essential fatty acid. About I0g of linoleic acid is ingested daily in adults. A small part of this intake is converted by elongation and desaturation in liver to arachidonic acid ( eicosatetraenoicacid ) and to some extent to dihomo -y-linoleic acid. Since the total daily excretion of prostaglandins and their metabolites is only about I mg. Rapidly removed from circulation. Upto 90% of PGs are destroyed in liver.

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