have a compiled information on prostaglandin role in platelete aggregation, for under graduate students....

2. ROLE OF PROSTAGALNDIN
IN PLATELETS
AGGREGATION
ASSIGNMENT FOR PHARMACOLOGY
MUHAMMAD OWIAS
ROLL NO 130450

3. AUTOCOIDS
 Autacoids or "autocoids" are biological factors which act like local
hormones, have a brief duration, and act near the site of synthesis.
The word autacoids comes from the Greek "Autos" (self) and "Acos"
(remedy).
 EXAMPLES OF AUTOCOIDS: histamine, serotonin,
prostaglandins, kinins etc.

4. WHAT IS PLATELET AGGREGATION?
 The clumping together of platelets in the blood. Platelet
aggregation is part of the sequence of events leading to the
formation of a thrombus (clot).
 PLATELET: a small colorless disc-shaped cell fragment without a
nucleus, found in large numbers in blood and involved in clotting.

5. PROSTAGLANDINS
 The prostaglandins (PG) are a large family of structurally
similar compounds that have potent and specific biological
action. They are 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.

6. BIO SY NTHE SIS OF PROSTAGL ANDINS

7. PROSTAGLANDINS
Prostaglandins have two main derivatives.
1.) Prostacylcins.
2.) Thromboxanes.
 Prostacyclins:. Prostacyclins are powerful locally acting vasodilators
and inhibit the aggregation of blood platelets. They are synthesized in the walls
of blood vessels and serve the physiological function of preventing needless
clot formation, as well as regulating the contraction of smooth muscle tissue

8. PROSTAGLANDINS
 Thromboxane: (produced by platelet cells) are vasoconstrictors and
facilitate platelet aggregation. Their name comes from their role in clot
formation (thrombosis).

10. THROMBOXANE AND
PROSTACYLCLIN
 Platelets express high level of the enzyme thromboxane synthase but do not
contain prostacyclin synthase. Therefore TxA2 is the chief eicosanoid product of
platelets.
 In contrast the vascular endothelium lacks thromboxane synthase but expresses
a prostacyclin synthase. Therefore PGI2 is the primary eicosanoid product of
vascular endothelium.
 The local balance between TxA2 and PGI2 levels is critical in the regulations of
systemic blood pressure and Thrombogenesis. Imbalances can lead to hypertension,
ischemia, thrombosis, coagulopathy, myocardial infarction and stroke.

11. THROMBOXANE AND
PROSTACYLCLIN
 Low concentrations of PGE 2 enhance (via EP 3), whereas higher
concentrations inhibit (via IP), platelet aggregation.
 Both PGD 2 and PGI 2 inhibit aggregation via, respectively, DP 1 and IP-
dependent elevation in cAMP generation.
 TXA 2 is the major product of COX-1, the only COX isoform expressed in
mature platelets. It induces shape change through G12/G13 mediated Rho-Rho
kinase dependent regulation of myosin light-chain phosphorylation and aggregation
through Gq dependent activation of PKC.

12. Eicosanoid
Major Site(s) of
Synthesis Major Biological Activities
PGD2 mast cells
inhibits platelet and leukocyte aggregation, decreases. induces
vasodilation and production of cAMP
PGE2 kidney, spleen, heart
increases vasodilation and cAMP production, enhancement of the
effects of bradykinin and histamine, induction of uterine contractions
and of platelet aggregation; decreases,
PGF2α kidney, spleen, heart
increases vasoconstriction, bronchoconstriction and smooth muscle
contraction
PGI2
heart, vascular
endothelial cells
inhibits platelet and leukocyte aggregation, induces vasodilation and
production of cAMP
TXA2 platelets
induces platelet aggregation, vasoconstriction, lymphocyte
proliferation and bronchoconstriction

13. DRUG USED FOR
ANTITHROMBOGENIC EFFECT:
 ASPIRINE (NSAID):
 It inhibits COX-1(and thus TXA2 synthesis) in platelets and COX-2
(and thus PGI2 synthesis) in endothelial cells by irreversible
accylation of these enzyme.
 When COX-1 is inhibited in platelets it can not be over come as they
don’t have a nuclei.
And when COX-2 is inhibited in endothelial cells as they have a nuclei
so can regenerate more COX-2 enzymes.

14. REFERENCES
 Marieb, Elaine Nicpon; Hoehn, Katja (2010). Human Anatomy & Physiology
(8th ed.). San Francisco: Benjamin Cummings. pp. 649–50.
 Clemetson, Kenneth J. "Platelets And Primary Haemostasis." Thrombosis
Research 129.3 (2012): 220-224
 Lassila, Riitta (2012). "New Insights Into Von Willebrand Disease And Platelet
Function". Seminars in Thrombosis & Hemostasis 38.1: 55–63.
 dr_van/new-style-prostaglandins?qid=3ea9293d-6c74-4006-806b-
ad551691596b&v=qf1&b=&from search=3.