Prostaglandins

Question 1

Membrane lipids make arachidonic acid. Arachidonic acid makes what two things?

Leukotrienes has an association to?

Answer 1

Prostaglandins and leukotrienes

Asthma

Question 2

Prostaglandins make

Arachidonic acid is considered

Answer 2

Thromboxanes and prostacyclin

The most common precursor of eicosanoids

Question 3

What 3 things are collectively referred to as eicosanoids?

Answer 3

Prostaglandins, leukotrienes, and thromboxanes

Question 4

4 ways eicosanoids differ from hormones

Answer 4

1. Eicosanoids are synthesized in all cells
2. They act locally (not systemically)
3. They have extremely short half lives
4. You only need a very small concentration to elicit desired effect

Question 5

Explain the following two types of eicosanoids:

1. Procoagulant
2. Anticoagulant

Answer 5

1. Platelets synthesize an eicosanoid thromboxane A2; promotes platelet aggregation and vasoconstriction locally
2. Vascular endothelial cells synthesize an eicosanoid prostacyclin PGl2; inhibits platelet aggregation and stimulates vasodilation

Question 6

1. What produces arachidonic acid?
2. Where is arachidonic acid stored?
3. Released by?

Answer 6

1. Linoleic acid
2. Phospholipids
3. Activated phospholipase (usually A2)

Question 7

1. What enzyme is required for synthesis of leukotrienes?

2. What enzyme is required for synthesis of prostaglandins and thromboxanes?

Answer 7

1. Lipoxygenase

2. Cyclooxygenase

Question 8

1. Steroids/glucocorticoids target what enzyme?
2. NSAIDS target what enzyme?

~what does it mean by “target what enzyme”

Answer 8

1. Phospholipase A2
2. Cyclooxygenase

~means these drugs upregulate the synthesis of an inhibitor of these enzymes

Question 9

1. Function of glucocorticoids?
2. Acts at the level of
3. Down regulates the transcription of ?

Answer 9

1. Minimize inflammatory response (asthma, etc.)
2. Gene expression
3. COX2

Question 10

1. NSAIDS inhibit
   * 2. What is COX2
2. So many function of aspirin?

Answer 10

1. COX (so no formation of prostacyclins or thromboxanes)
2. Inducible version of cyclooxygenase that causes pain, head, redness, and swelling and fever
3. Inhibit COX2 ~ aspirin is an NSAID

Question 11

So upregulation of COX2 will cause?

Answer 11

Inflammatory response

Question 12

Function of corticosteroids?

Answer 12

Inhibit the production/gene expression of COX2 enzymes

Question 13

Explain how aspirin could induce an asthmatic response

Answer 13

Aspirin blocks COX2. COX2 produces prostaglandins and thromboxanes - so inhibition of COX2 can force intermediates to produce leukotrienes which is involved in the asthmatic response

Question 14

What kind of inhibition does aspirin do to cyclooxygenase (both COX1 and COX2)

Effect this has on platelets

How long does aspirin inhibition persist on platelet

Answer 14

Suicide inhibition (irreversible)

Platelets are reduced in their thrombogenic potential - no thromboxane production since platelets have no nucleus

7-10 days

Question 15

Aspirin effect on vascular endothelial cells

Answer 15

These have a nucleus so you can synthesize new COX1 and COX2; so prostacyclin is produced as well just at a reduced rate

Question 16

Explain why all these explains why aspirin is used for heart disease

Answer 16

Reduces clotting to help prevent formation of clot in the atherosclerotic plague

Question 17

Explain relationship between prostaglandins and blood coagulation in healthy endothelium

Answer 17

Endothelium releases prostacyclin into blood plasma, plasma prostacyclin activates cAMP system on platelets, cAMP inhibits release of granules containing platelet aggregating agents (ADP + serotonin)

Question 18

Explain relationship between prostaglandins and blood coagulation in injured endothelium

Answer 18

Release of thromboxane stimulates PIP2 system. IP3, DAG and Ca2+ stimulate release of granules containing platelet aggregating agents. Further enhances synthesis of additional thromboxane to stimulate other platelets in area to aggregate

Question 19

Explain relationship between prostaglandins and blood coagulation in hemostasis (stopping of blood flow)

Answer 19

Balance between levels of prostacyclin (cAMP agonist) and thromboxane (PIP2 agonist) dictate platelet aggregation status