Prostaglandins, PG, Biochemistry, Medicines, Subscribe to my youtube channel for such great contents www.youtube.com/c/AwesomeBiochemistry

1. Prostaglandins
DR. KALPESH NAKARANI

2. History
 Discovered by – Euler (1933)
Biosynthetic pathway – Samuelsson (Noble prize, 1982)
Chemical synthesis – Elias Corey (Noble prize, 1990)

3. Overview
20C Compound (derived from Arachidonic acid)
PGs & related compounds (PGI, Tx, LT) – collectively known as eicosanoids.
(Greek: eikosi=20)
Also known as ‘Local hormones’
Site of production
Site of action
Metabolism

4. Chemistry
 Derivatives of ‘Prostanoic acid’ (Hypothetical compound)
20C Saturated FA
8th & 12th Carbon join to form ring (Cyclopentane ring)
Trans double bond at C-13 & -OH group at C-15

5. Cyclopentane ring Side chain
Denotes different type of action Denotes different potency of the product
Identified by A, B, C….etc (Based on type of
Cyclopentane ring)
e.g.
PGD PGF
PGE PGG
Identified by subscript numbers 1, 2, 3 (Based on
number of double bonds in side chain)
e.g.
PGE1  one double bond
PGE2  two double bond
PGE3  three double bond
Different type of actions Same action but difference in potency

6. Classification
Eicosanoids
Leukotriens & LipoxinsProstanoids
ThromboxanesProstacyclinsProstaglandins
PG-E group: PGE-1, PGE-2 and PGE 3
PG-F group: PGF1α, PGF2α and PGF3α
PG-A group: PG-A1, PG-A2, 19-OH PG-A1, 19-OH PG-A2
PG-B group: PG-B1, PG-B2, 19-OH PG-B1, 19-OH PG-B2
Note
• PG-E  Soluble in ether
• PG-F  Soluble in phosphate buffer
(Fosfat, in Swedish)
• All other PGs discovered later were
denoted by a letter- PGA, PGB etc)

7. Synthesis
Membrane Phospholipid
Phospholipase A2
Arachidonic Acid
PG G2 (unstable)
PG H2 (unstable)
Peroxidase
Cyclooxygenase
Prostaglandin
Synthase complex
O2
2GSH
G-S-S-G
Cyclic endoperoxides
Prostanoids
Leukotrienes
&
Lipoxins

8. Prostanoids
PG H2 (unstable)
PG I2
PG E2
Tx A2
PG D2
6-keto PGF1α Tx B2
Prostacyclin synthase Thromboxane SynthaseIsomerase

9. LTA4 epoxide
hydrolase
Leukotrienes
Arachidonic acid
12-HPETE
12-LOX
15-HPETE
15-LOX
5-HPETE
5-LOX
O2
LT A4
LT C4
LT D4
LT E4
Glutathione-s-transferase
ϒ-Glutamyl transpeptidase
Cysteinyl-glycine dipeptidase
H2O
Glutamic acid
Glycine
Glutathione
12-HETE 15-HETE5-HETE
5-LOX
Lipoxins
(e.g.LxA4)
LT B4
H2O
Peroxidase

11. Mechanism of action

12.  PG endoperoxides (G2 and H2) are inherently vasoconstrictor, but often produce vasodilatation
or a biphasic response due to rapid conversion to other PGs, especially PGI2, in the blood vessels
themselves.
 Clinical role:
1. PGE2 & PGI2 are believed to be continuously produced locally in the ductus arteriosus during foetal
life – keep it patent.

13. TXA2 produced by platelets and PGI2 produced by vascular endothelium probably constitute a
mutually antagonistic system
 Clinical role:
1. Aspirin inhibits both, then why it exerts only anti-aggregatory role?
Organ PGE2 PGF2α PGI2 TXA2
Platelets ~ Anti-
aggregatory
Pro-aggregatory

14.  Clinical role:
1. PGs mediate initiation and progression of labour. Aspirin has been found to delay the initiation of
labour and also prolongs its duration.
2. PGs  uncoordinated uterine contractions compress blood vessels  uterine ischemia  pain
(Dysmenorrhoea). Aspirin is highly effective treatment.
Organ PGE2 PGF2α PGI2 TXA2
Uterus In vivo-contraction
In vitro-relaxation of non
gravid uterus
Softening of cervix
In vivo & in vitro –
contraction
Softening of cervix
- -

15.  Asthmatics are more sensitive to constrictor as well as dilator effects of PGs.
 Clinical Role:
1. Aspirin induces asthma.
Organ PGE2 PGF2α PGI2 TXA2
Bronchi Dilatation Constriction Mild dilatation Constriction

16.  PGs appear to play a role in the growth of colonic polyps and cancer. Association of low
incidence of colon cancer with regular intake of aspirin is now established.
 Clinical role:
1. NSAIDS can induce gastric ulcer due to loss of this function by COX-1 inhibition.
Organ PGE2 PGF2α PGI2 TXA2
Stomach ↓ acid secretion
↑ mucus production
↓ acid secretion (weak)
Mucosal VD
Intestine ↑ peristalsis
↑ Cl- & water secretion
Spasmogenic Weak spasmogenic Weak spasmogenic

17.  PGs appear to function as intra-renal regulators of blood flow as well as tubular reabsorption
in kidney. The NSAIDs tend to retain salt and water.
 Bartter's syndrome, characterized by decreased sensitivity to angiotensin II is associated with
increased PG production. many of the manifestations are improved by prolonged use of NSAIDs.
Organ PGE2 PGF2α PGI2 TXA2
Kidney • Natriuresis
• ↓ Cl- reabsorption
• Inhibit ADH action  Diuresis
• VD  ↑ GFR & ↑ RPF
• Renin release
Natriuresis
VD
Renin release
VC

18. Organ PGE2 PGF2α PGI2 TXA2
Metabolic effects • Lipolysis
• Insulin like effect
• PTH like effect
• Thyrotropin ike effect

19. Pain

20. Limitations of use of PGs as drugs
 Short duration of action
 Lack of tissue specificity
 PG analogues: Introduction of –CH3 at 15th position leads to longer duration of action as well
as improvement of tissue specificity.

21. Thank You