Eicosanoids & Prostaglandins

Question 1

Histamine

Answer 1

Released from white cells known as “mast cells”

Degranulation of mast cells occurs in response to injury or presence of an allergen

Blood vessels dilate, capillaries become more permeable

Redness, swelling, itching

Question 2

Prostaglandins

Answer 2

Made at site of tissue damage or infection

Made from arachidonic acid

Found in cell membranes

Cause blood vessels to dilate and capillaries to become more permeable

Affect blood pressure and sensation of pain, others work in opposite ways

Can promote clotting (thromboxane) or reduce clotting (prostacyclin)

Question 3

eicosanoids

Answer 3

Signaling molecule

They exert complex control over many bodily systems; mainly in growth during and after physical activity, inflammation or immunity after the intake of toxic compounds and pathogens, and as messengers in the central nervous system. The networks of controls that depend upon eicosanoids are among the most complex in the human body.

Question 4

How are various prostaglandins made different from each other structurally?

Answer 4

Substitutions on the 5 membered cyclopentane ring

Question 5

Can RBC make prostaglandins?

Answer 5

No

Question 6

What releases arachidonic acid?

Answer 6

Phospholipase A2 is a membrane-bound enzyme that acts on membrane phospholipid to release arachidonic acid (phospholipase C can also release it but from a different site)

Question 7

NSAIDs

Answer 7

Exert their effects through inhibition of COX

No COX–>No PGE2–>No stomach protection (gastric mucosa)–>ulcers

Question 8

Lungs inactivate PG’s how?

How is Thromboxane and prostacyclin inactivated?

Answer 8

Lungs inactivate any PG’s that are floating around via 15-OH-PGDH

Thromboxane and prostacyclin inactivated via WATER

Question 9

Prostacyclins

Answer 9

vasodilators and inhibit the aggregation of blood platelets

Question 10

Thromboxanes

Answer 10

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

Question 11

What are eicosanoids?

Answer 11

Family of lipid mediators derived from oxidative transformation of 20-carbon polyunsaturated fatty acids. Eicosanoids include prostaglandins, thromboxane and leukotrienes as the main family members. Eicosanoids are autacoid mediators

Question 12

Autacoids

Answer 12

Short lives

Localized

Made all over body by nearly all tissues (unlike hormones)

Question 13

What pathways use autacoid mediators?

Answer 13

Autocrine and paracrine

Question 14

Cofactors for COX

Answer 14

Iron, O2

Question 15

What is required for prostaglandin and thromboxane synthesis?

Answer 15

O2 and arachidonic acid (AA)

Question 16

PGE2/PGI2 + EP2, EP4, IP= affect on smooth muscle

Answer 16

AC–>cAMP–>relaxing smooth muscle (vasodilating blood vessels)

Question 17

PGF2+FP or TXA2+TP effect on smooth muscle

Answer 17

Assemble –> IP3–>↑Ca 2+ in cytosol–> contract (constrict smooth muscle)

Question 18

Excess TxA2: TP

Deficient PGI2:IP

Answer 18

Excess TxA2–> Angina pectoris (coronary vasoconstriction)

Symptoms: pain in chest

Question 19

Excess of PGE2 (GI)

Answer 19

Diarrhea, cramps

Deficit of PGE2 (GI)=ulcers

Question 20

Prostaglandins active in the reproductive system and role

Answer 20

PGE2:EP
PGF2α:FP

Dilate the cervix, contract the uterus, parturition (delivery)

Deficit: delayed birth
Excess: pre-mature labor, pre-mature birth

Question 21

PG active in neonatal development and role

Answer 21

PGE2:EP (EP4)

Maintains ductus arteriosus in the fetus which allows maternal blood to bypass immature fetal lungs. Mature neonatal lungs will metabolize PGE2 which will close the ductus arteriosus

Question 22

Prostaglandins in renal physiology and role

Answer 22

COX-2 always present in kidney along with COX-1.

PGE2/EP receptor role: renal blood flow, filtration and Na + H2O excretion in the kidney

Question 23

Decifit of PG (kidney)

Answer 23

Leads to Na+ and H2O retention (edema), mild hypertension (elevated blood pressure)

Question 24

Prostaglandin role in inflammation

Answer 24

PGI2 (prostacyclin) causes vasodilation and decreased platelet aggregation

PGE2 increases vascular permeability, causes pain sensitization, and can cause fever

Question 25

Negative effects of PG in inflammation

Answer 25

Erythema, edema, pain. If COX-2 is induced all symptoms are increased, thus NSAIDs inhibit COX activity

Question 26

What stimulates platelets to make TxA2?

Answer 26

Collagen Blood platelets get exposed to collagen-->collagen stimulates TxA2 formation by platelets

Question 27

What stops the process of clotting from spreading throughout the blood stream? What keeps it local?

Answer 27

The stimulus (collagen) is local...and another eicosanoid- PGI2 (prostacyclin)-made by endothelial cells opposes the actions of TxA2 on blood vessels and platelets

Question 28

What is the importance of COX-2 in thrombosis?

Answer 28

Endothelial cells have a nucleus and can therefore induce production of COX-2 which will increase production of prostacyclin. This will vasodilate and inhibit platelet aggregation allowing blood flow past plaque. Platelets cannot induce production of COX-2 and therefore cannot counteract this benefit

Question 29

True or False Platelets have the capability for de novo translation of proteins

Answer 29

False

Question 30

True or False Endothelial cells have the capability of de novo transcription and translation of proteins

Answer 30

True COX-2 can be induced in endothelial cells

Question 31

How can the build up of PGI2 preventing thrombosis be a negative?

Answer 31

Part of underlying disease progression in atherosclerosis...inflammation. If endothelial cells' COX-2 and COX-1 fails to maintain adequate PGI2 synthesis, it may tip the balance in favor of vessel occlusion (the blockage or closing of a blood vessel) if a plaque ruptures...this is what causes heart attacks

Question 32

What is the benefit of eating an omega 3 fatty acid diet on heart disease?

Answer 32

Some eicosapentaenoic acid eventually replaces some arachidonic acid which weakens the effects of thromboxane A2 which leads to weaker vasoconstriction and weaker platelet aggregation Eicosapentaenoic acid-->TxA3 (weaker vasoconstricter than TxA2) Heart disease=too much TxA2

Question 33

COX1, PGs and Inflammation

Answer 33

1. Inflammation stimulates AA release 2. COX-1 converts AA into PGE2 3. PGE2 causes symptoms 4. Inflammation induces COX-2 5. Converts AA into PGE2 6. Amplifies symptoms * makes it worse but good for infections * Symptoms of inflammation: erythema (redness), edema (swelling), pain

Question 34

Balance: PGI2 (endothelial cells) vs TxA2 (platelets)

Answer 34

PGI2__________TxA2 Δ PGI2: endothelial (relax blood vessels, inhibit platelet formation) TxA2: platelets (constrict blood vessels, amplifies platelet aggregation) Too much=block blood vessel

Question 35

Endothelial cells vs Platelets

Answer 35

Endothelial Cells vs Platelets COX-1 / COX-1 PGI2 synthase / Tx Synthase PGI2 / TxA2 TP & IP receptors / " " Vasodilation (BP down)/ Vasoconstriction (BP up) Inhibits platelet aggregation/ Causes platelet aggregation

Question 36

Atherosclerosis

Answer 36

The build-up of fats, cholesterol, and other substances in and on the artery walls. Atherosclerosis can cause more PGI2 formation (to try to unclog artery)

Question 37

Renal physiology

Answer 37

Filtering blood is so important in KIDNEY that both COX1/COX2 are used PGE2:EP Deficit: Na+ & H2O retention(edema)-->Mild hypertension *More common in elderly