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BIO CHEMICAL FUNCTIONSOF

EICOSANOIDS

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Arachidonic acid derivatives

Act as local hormonesThey include

prostaglandins(PGs)

prostacylins

Thrombanes(Txs)

Leukotrienes(LTs)HETE

HPETE

Lipoixn

Among these PGs ,TXs,LTs have important

functions

Introduction

EICOSANOIDS

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Smooth muscles

Vascular smooth muscles

PGE2,PG2 relax arteriolar smooth

muscles.

Increase blood flow.

Useful in treatment of hypertension.

TXA2 & PGF2 are vasoconstrictors.

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Smooth muscles..

Gastrointestinal tract

Longitudinal muscles contracted by

PGE2 & PGF2.

Circular muscles contracted by PGF2

& PG2.

Cause colicky cramps

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Respiratory tract

PGE2 is a bronchodilator.

PGF2 alpha & TXA2 are

bronchoconstictors & primary

mediaters in asthma.

corticosteroids inhibit the formation of

eicosanoids relievs asthma.

Smooth muscles

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Gastrointestinal

system

Cycloprotection.

PGE2 bind Gi protetin via EP3receptors.

Decrease CAMP level.

CAMP depended protein kinase

action decrease.

H+Secretion decrease at K+- H+ATPase pump.

NSAIDS PGs synthesis.

Cause ulcer.

Synthetic analog of PGE2 used in

treatment for ulcer.

ATPCAMP

K+

H+

AC

Ach receptor

histamine

receptor

PGE2

EP3

Protein kinase

Gi

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RENAL SYSTEM

PGE1,PGE2& PGI2increase GFR by vasodilation.

Increase water & Na+ excretion.

PGE2& PGI2increase Renin secretion.

TXA2causes intra renal vasoconstriction ADH - like

effect.

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IMMUNE SYSTEM

Chemotaxis and migration5-HETE & LTD, mediate migration of

neutrophil & eosinophils.

Induce release lysosomal enzymes.

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Cell mediated immunity & organ transplantation

Acute organ transplant rejection is a cell mediatedimmune response.

PGE2 & PEI2 prevent T-cell proliferation &

rejection.

Corticosteroids prevents acute organ transplantrejection.

IMMUNE SYSTEM.

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T-Cell

T-Cell

Macrophage

Antigen

presenting cell

Lymphocytes

PGI2

PGE2

Corticosteriods-

PGI2

PGE2

Corticosteriods-

LTB4

TXA2 +

PGI2,PGE2-

LTD4,LTB4+LTD4,LTB4+

IL-1

IL-2

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Inflammation

Is response of body for

Infection

InjuryDestroying the infection agent.

Inflammatory process are:

Redness &pain:- by PGE2 & LB4 vasodilators

Swelling & heat :- LTB4 increase permeability

of vessels.

:- Plasma leak out & swelling

IMMUNE SYSTEM.

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Rheumatic arthritis

Due to deposition of immune complex

in joints.

LTs cause T-cell proliferation.

Corticosteroids inhibit LTS

formation.

IMMUNE SYSTEM.

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REPRODUCTIVESYSTEM

MALE REPRODUCTIVE SYSTEM

PGE1 increase contraction of seminal vesicle.

Synthetic analog of PGE2 is use in treatment of

erectile dysfunction in spinal cord injury.

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Labor

PGE2 & PGF2 & promote uterine contraction.Soften the cervix by changes in collagen

synthesis.

Inducing labor.

Abortion

Induce abortion at any stage of pregnant state.

Clinically used in abortion.

FEMALE REPROCUTIVE SYSTEM

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FEMALE REPROCUTIVE

SYSTEM..

Dysmenorrhoea It is painful menstruation.

PGE2 alpha & PGF2 alpha are

formed during menstruation. Cause painful contraction of

uterus.

Aspirin relieves the pain.

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PATENCY OF DUCTUS

ARTERIOSUS IN FOETUS

PGE2 maintain patency of ductusarteriosus before birth.

Infusion of PGE2 cause maintain ductusarteriosus after birth.

PGE2 inhibiters used to close this after

birth.

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BLOOD

RBC

PGE2 decrease deform capacity of RBC

membrane.

PlateletsTXA2 platelet aggregator.

PGE1 and PGI2 inhibit platelet aggregation.

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PLATELETACTIVATION&

THROMBOSIS

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PLA2

PL

Arachidonic acid

TXA2

PLC

PIP3

DAGIP3 +

ThrombinCollagen

Collagen

TXA2

PGI2ADP

Receptors

TXA2

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Ca2+

Ca 2+Ca 2+

Ca 2+

PGI2

AC

ATP

CAMP

PK

Myosin

P

Actin+

P

Actin

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DAG

PKCP

Fibrinogen

Fibrinogen

Pleckstrin Pleckstrin

ATP

Signal

Granules

Gp

11-b

Gp

11-a

Gp11-b Gp

11-a

ADP

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PLATELET ACTIVATION& THROMBOSIS

1) Adhension of platelets to collagen

Receptors forPGI2,collagen,TXA2,thrombin & ADP found in plateletsmembrane.

Damaged blood capillaries exposecollagen.

Platelet adhere to collagen.

Activate phospholipase A2 (PLA2)

It release arachidonic acid & TXA2formed.

Thrombin augment TXA activity

BLOOD..

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TXA2 & receptor activate PLC as autocrine

hormone.Which release (IP3) inositol triphosphate

and Diacyl Glycerol.

IP3 increase intracellural Ca2+.

PGI2 increase intracellular CAMP asparacrine hormone.

CAMP decrease intracellular Ca2+.

BLOOD..

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CENETRAL & PERIPHERAL

NERVOUS SYSTEM

Fever

PGE1 & PGE2 produce in hypothalamus.

Increase body temperature.Cause fever.

Pain

PGE2 &PGD2 enhance duration & intensity ofpain.

Sleep

PGD2 induce slow -wave & natural sleep.

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Neurotransmission

PGE compound inhibit nor- epinehriae at synapse

some prostaglandins act as neurotransmitters

prostaglandins

prostaglandins

receptor

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THE ENDThank You