Lipid Mediators

Question 1

Autacoid

Answer 1

Rapidly synthesized in response to a signal, acts quickly and locally

Question 2

Eicosanoid

Answer 2

20-carbon arachidonic acid derived autacoid

Pleiotropic effects

Ex: prostanoids and leukotrienes

Question 3

What enzymes convert arachidonic acid to a prostaglandin and thromboxane A2?

Answer 3

Cyclooxygenases (COX1 and COX2)

Question 4

Where does arachidonic acid come from?

Answer 4

Phospholipase A2 (PLA2) liberates it from the cell membrane

Question 5

What enzyme converts arachidonic acid to leukotrienes?

Answer 5

5-lipoxygenase (5-LO)

Question 6

What inhibits the cyclooxygenase pathway?

Answer 6

COX-1 and COX-2 inhibitors

Aspirin (and indomethacin): COX1 and COX2

VIOXX: only COX2

Question 7

LTB4

Answer 7

Neutrophil chemotaxis/adherence to endothelium

Produced by leukocytes, mast cells, endothelial cells

(Leukotriene)

Question 8

LTC4, LTD4, LTE4

Answer 8

Asthma

“anaphylaxis”

Edema, bronchospasm, mucus secretion, recruit inflammatory cels

Produced by leukocytes, mast cells, endothelial cells

(Leukotriene)

Question 9

Platelet activating factor (PAF)

Answer 9

Neutrophil-activating (chemotaxis, endothelial adhesion)

Located on endothelial membrane and binds neutrophil

Vasodilation, edema

Released by leukocytes, mast cells, endothelial cells

Question 10

COX1

Answer 10

Constitutively expressed

Homeostasis

Maintenance of renal/GI blood flow

Anti-thrombotic

Question 11

Lipid mediators and what cells release them

Answer 11

Prostaglandins: mast cells, leukocytes

Leukotrienes: mast cells, leukocytes, endothelial cells

PAF: mast cells, leukocytes, endothelial cells

Question 12

COX2

Answer 12

Inducible

Inflammation

(Macrophages come into contact with microbe/LPS and begin expressing COX2)

Question 13

PGH2

Answer 13

Major intermediate produced when arachidonic acid converted by COX1 and COX 2 (in 2 steps)

Goes on to produce PGD2, PGE2, PGF2a, PGH2, PGI2, TxA2

Question 14

PGE2

Answer 14

Inflammation

Fever, pain, vasodilation, edema, smooth muscle contraction/dilation

Produced in macrophages, mast cells

Question 15

PGI2

Answer 15

Vasodilation

Anti-coagulation

Produced in endothelium

(always TxA2 vs. PGI2)

Question 16

Thromboxane A2

Answer 16

Vasoconstriction

Pro-thrombotic

Released from platelets only

(always TxA2 vs. PGI2)

Question 17

How exactly do prostaglandins work?

Answer 17

Bind to G-protein coupled receptors

Tissue specific expression (PGD2, PGF2a, etc) with tissue specific receptors

Paracrine

Question 18

PGD2

Answer 18

Regulates sleep-wake cycle in brain, inhibits platelet aggregation, induces relaxation of smooth muslce, recruits inflammatory cells (eosinophils)

Produced in macrophages, mast cells

Question 19

Aspirin

Answer 19

Covalently binds, and inactivates COX1 and COX2

Anti-inflammatory, but because it also binds COX1, can cause GI ulcers

Reduced risk of stroke, decreased severity of MI

Question 20

VIOXX

Answer 20

Selectively binds COX2 (site to block COX2 is smaller than COX1)

Causes blood clots because now relatively more TxA2 than PGI2