2. ο Postaglandins & their related compounds
prostacyclins (PGI), thromboxanes (TXA),
leukotrienes (LT) & lipoxins are collectively
known as eicosaniods, they all contain 20C.
ο Structure of prostaglandins:
ο Prostaglandins are derivatives of 20-carbon
fatty acid - prostanoic acid, hence known as
prostanoids.
3. ο This has a cyclopentane ring (formed by
carbon atoms 8 to 12) & two side chains, with
carboxyl group on one side.
ο Prostaglandins differ in their structure due to
substituent group & double bond on
cyclopentane ring.
ο Most important prostaglandins (PGF2 &
PGF2Ξ±), prostacyclins (PGI2), thromboxanes
(TXA2) & leukotrienes (LTA4).
4.
5. ο Arachidonic acid (5,8,11,14 - eicosatetraenoic
acid) is the precursor for most of the
prostaglandins in humans.
ο It occurs in the endoplasmic reticulum.
ο Release of arachidonic acid from membrane
bound phospholipids by phospholipase A2.
ο It occurs due to a specific stimuli by
hormones β epinephrine or bradykinin.
6. ο Oxidation & cyclization of arachidonic acid
to PGG2 which is then converted to PGH2 by
peroxidase.
ο PGH2 serves as the immediate precursor for
the synthesis of a number of prostaglandins,
including prostacyclins & thromboxane.
ο This is known as cyclic pathway of
arachidonic acid.
7.
8. ο Cyclooxygenase β a suicide enzyme.
ο Prostaglandin synthesis can be partly
controlled by suicidal activity of the enzyme
cyclooxygenase.
ο This enzyme is capable of undergoing self-
catalysed destruction to switch off PG
synthesis.
9. ο Corticosteroids (e.g. cortisol) prevent the
formation of arachidonic acid by inhibiting
the enzyme phospholipase A2.
ο Anti-inflammatory drugs inhibit the synthesis
of prostaglandins, prostacyclins &
thromboxane.
ο They block the action of cyclooxygenase.
ο Aspirin irreversibly inhibits cyclooxygenase.
10. ο All the eicosanoids are metabolized rapidly.
ο Degradation occur in lung & liver.
ο Two enzymes, namely 15-Ξ±-hydroxy PG
dehydrogenase & 13-PG reductase, convert
hydroxyl group at C15 to keto group & then
to C13 and C14 dihydroderivative.
11. ο Prostaglandins act as local hormones.
ο PGs are produced in almost all the tissues.
ο PGs are not stored & they are degraded to
inactive products at the site of their
production.
ο PGs are produced in very small amounts &
have low half-lives.
12. ο Regulation of blood pressure:
ο The prostaglandins (PGE, PGA & PGl2) are
vasodilator in function.
ο This results in increased blood flow and
decreased peripheral resistance to lower the
blood pressure.
ο PGs serve as agents in the treatment of
hypertension.
13. ο Inflammation:
ο PGEI & PGE2 induce the symptoms of
inflammation (redness, swelling, edema etc.)
due to arteriolar vasodilation.
ο PGs are natural mediators of inflammatory
reactions of rheumatoid arthritis, psoriasis,
conjunctivitis etc.
ο Corticosteroids are used to treat these
inflammatory reactions, since they inhibit
prostaglandin synthesis.
14. ο Reproduction:
ο PGE2 & PGF2 are used for the medical termination of
pregnancy & induction of Iabor.
ο Pain and fever:
ο Pyrogens (fever producing agents) promote
prostaglandin synthesis leading to the formation of
PGE2 in hypothalamus-regulation of body temperature.
ο PGE2 along with histamine & bradykinin cause pain.
ο Migraine is also due to PGE2.
ο Aspirin & other non-steroidal drugs inhibit PG synthesis
& thus control fever & relieve pain.
15. ο Regulation of gastric secretion:
ο Prostaglandins (PGE) inhibit gastric secretion.
ο PGs are used for the treatment of gastric ulcers.
ο PGs stimulate pancreatic secretion & increase
the motility of intestine which often causes
diarrhea.
ο Influence on immune system:
ο Macrophages secrete PGE which decreases the
immunological functions of B-& T-lymphocytes.
16. ο Effects on respiratory function:
ο PGE is a bronchodilator whereas PGF acts
as a constrictor of bronchial smooth
muscles.
ο PGE & PGF oppose the actions of each other
in the lungs.
ο PGEI & PGE2 are used in the treatment of
asthma.
17. ο Influence on renal functions:
ο PGE increases glomerular filtration rate &
promotes urine output.
ο Excretion of Na+ & K+ is also increased by PGE.
ο Effects on metabolism:
ο Prostaglandins influence certain metabolic
reactions, through the mediation of cAMP.
ο PGE decrease lipolysis, increases glycogen
formation & promotes calcium mobilization.
18. ο Platelet aggregation & thrombosis:
ο The prostaglandins β prostacyclins (PGI2),
inhibit platelet aggregation.
ο Thromboxanes (TXA2) & prostaglandin E2
promote platelet aggregation & blood
clotting that might lead to thrombosis.
ο Mechanism of action of PGs:
ο PGE increases cAMP & PGF increases cGMP.
19. ο They are used in the treatment of gastric
ulcers, hypertension, thrombosis, asthma etc.
ο Prostaglandins are also employed in the
medical termination of pregnancy,
prevention of conception, induction of labor
etc.
20. ο Leukotrienes are synthesized by leucocytes,
mast cells, lung, heart, spleen etc., by
lipoxygenase pathway of arachidonic acid.
ο Leukotrienes (A4, B4, C4, D4 & E4) are
synthesized through the intermediate, 5-
hydroperoxyeicosatetraenoic acid (5-HPETE).
21.
22. ο Leukotrienes (C4, D4 & E4) are components of
slow-reacting substances of anaphylaxis (SRS-
A), released after immunological challenge.
ο SRS-A is 100 -1,000 times more potent than
histamine or prostaglandins in its action as a
stimulant of allergic reactions.
ο Leukotrienes are implicated in asthma,
inflammatory reactions, hypersensitivity
(allergy) and heart attacks.
23. ο Leukotrienes cause contraction of smooth
muscles, bronchoconstriction,
vasoconstriction, adhesion of white blood
cells & release of lysosomal enzymes.
ο Lipoxins are involved in vasoactive &
immunoregulatory functions.