PROSTAGLANDINS

Dr. ASHOK KUMAR. JInternational Medical School

Management and Science UniversityMalaysia

EICOSANOIDS

20 Carbon containing

compounds

Prostaglandin,

thromboxane

leukotriene

“local” hormones

Most common

precursor Arachidonic

acid

CLASSIFICATION

Eicosanoids

Prostanoids(PG)

Prostaglandin

s(PG)

Prostacycl

ins(PGI)

Thromboxane

s(Tx)

Leucotrienes

Cyclooxygenase Lipoxygenase

Prostaglandins

First discovered in human semen by Ulf von Euler (of Sweden)•Isolated from prostate gland and hence named them as prostaglandin•Later realized that PGs are synthesized in almost all the tissues( exception erythrocytes)

considered to be derived from the

20 C cyclic saturated fatty

acid, prostanoic acid

The five carbon ring is saturatedAll naturally

occurring PGs have an alpha-oriented OH group at C15

According to the attachment of different substituent groups to the ring, PGs are named with capital letters such as A, B, E and F

PGA PGB PGC PGD

PGE PGF PGG & PGH PGI

PGF is designated as PGF α to denote the projection of the OH group at C9 in naturally occurring prostaglandins

PGG: Two oxygen atoms present at C9 and C 11 are bonded with hydroperoxide group at C15

PGH : Two oxygen atoms present at C9 and C 11 are bonded with hydroxyl group at C15

Depending on number of double bonds on the side chains different series (e.g. PGE1, PGE2, PGE3)

Series 1• Contain 1 double bond• Synthesized from Linolenic acid

Series 2

• Contains 2 double bonds• Most common variety• Synthesized from Arachidonic acid

Series 3• Contains 3 double bonds• Synthesized from Eicosa penta-enoic acid

Synthesis

Cycloxygenase

Phospholipase A2

AspirinIndomethacinlbuprofe(NSAID)

Corticisteroids

EpnephrineThrombinAngiotensin II Bradykinin Vasopressin

+

-

-

PGG and PGH are intermediates in the

synthesis

PGs are widely distributed in the body PGD2, PGE2, PGF2 and PGI2 and

thromboxane A2

Thromboxanes have 6 membered

oxane ring

• Function through G-protein coupled receptors

• Prostaglandins have only very short half life of about 30 seconds• Inactivated by the 15-hydroxy-prostaglandin-dehydrogenase• which converts 15-OH group to keto group

FUNCTIONS

• PGI2 • Vasodilatation dilatation• PGA and PGE class prostaglandins lower blood pressure• Inhibits platelet aggregation

Effects on CVS

Effects on Respiratory tract

PGF -BronchoconstrictionPGE -Bronchodilator

Effects on uterus

PGF2Inducing labor

Metabolic Effects

PGE2 decreases lipolysis,increases calcium mobilization from bone and glycogen synthesis

Effects Inflammation

Effects on GIT

PGE2 and D2

Involved in inflammatory response

PGE2 suppress gastric acid secretionused therapeutically in treatment of acid peptic diseaseDiarrhea is the side effect

Pain and fever

PGE2 • Produced in hypothalamus causes increased body

temperature• Involved in causing pain during inflammation

• First isolated from blood platelets, thrombocytes

• Capital letters – designate class• Subscript number denotes number

of double bonds

Thromboxanes [TX](Most common

TXA2)

Thromboxanes - FUNCTIONS

Increase platelet aggregation

Vasoconstriction

Smooth muscle contraction ; Bronchoconstriction

• Leukotrienes were so named because they were initially described in leucocytes

• Synthesized by leucocytes, mast cells, lung, heart, spleen etc.

Leukotrienes

FUNCTIONS

Role in inflammation and allergic reactions

Contraction of smooth muscles : Bronchoconstriction

Increases Chemotaxis

Thank you