Lipid Mediators Flashcards Preview

Block 1 lectures > Lipid Mediators > Flashcards

Flashcards in Lipid Mediators Deck (20):
1

Autacoid

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

2

Eicosanoid

20-carbon arachidonic acid derived autacoid

Pleiotropic effects

Ex: prostanoids and leukotrienes

3

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

Cyclooxygenases (COX1 and COX2)

4


Where does arachidonic acid come from?

Phospholipase A2 (PLA2) liberates it from the cell membrane

5

What enzyme converts arachidonic acid to leukotrienes?

5-lipoxygenase (5-LO)

6


What inhibits the cyclooxygenase pathway?


COX-1 and COX-2 inhibitors

Aspirin (and indomethacin): COX1 and COX2

VIOXX: only COX2

7

LTB4

Neutrophil chemotaxis/adherence to endothelium

Produced by leukocytes, mast cells, endothelial cells

(Leukotriene)

8


LTC4, LTD4, LTE4

Asthma

"anaphylaxis"

Edema, bronchospasm, mucus secretion, recruit inflammatory cels

Produced by leukocytes, mast cells, endothelial cells

(Leukotriene)

 

9

Platelet activating factor (PAF)

Neutrophil-activating (chemotaxis, endothelial adhesion)

Located on endothelial membrane and binds neutrophil

Vasodilation, edema

Released by leukocytes, mast cells, endothelial cells

10

COX1

Constitutively expressed

Homeostasis

Maintenance of renal/GI blood flow

Anti-thrombotic

11


Lipid mediators and what cells release them


Prostaglandins: mast cells, leukocytes

Leukotrienes: mast cells, leukocytes, endothelial cells

PAF: mast cells, leukocytes, endothelial cells

12

COX2

Inducible

Inflammation

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

13

PGH2

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

14

PGE2

Inflammation

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

Produced in macrophages, mast cells

15

PGI2

Vasodilation

Anti-coagulation

Produced in endothelium

(always TxA2 vs. PGI2)

16

Thromboxane A2

Vasoconstriction

Pro-thrombotic

Released from platelets only

(always TxA2 vs. PGI2)

17

How exactly do prostaglandins work?

Bind to G-protein coupled receptors

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

Paracrine

18


PGD2


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

Produced in macrophages, mast cells

19


Aspirin


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

20


VIOXX


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

Causes blood clots because now relatively more TxA2 than PGI2