MW L3 Eicosanoids

Question 1

Where do Eicosanoids come from?

3

Answer 1

Oxidation products of 20C fatty acids
(-arachidonic acids
-dihomo gamma-linolenic acid
-eicosapentaenoic)

Question 2

4 Classical eicosanoids

Answer 2

prostaglandins
prostacyclins
thromboxanes
leukotrienes

Question 3

4 non-classical eicosanoids

Answer 3

lipoxins
resolvins
isoprostanes
endocannabinoids

Question 4

What receptor type is for prostaglandins?

Answer 4

specific GPCRs for different prostaglandins

Question 5

What are the receptors PGE2?

Answer 5

EP1-EP2

Question 6

What is the receptor for PGI2?

Answer 6

IP

Question 7

EP2 and IP are couple to……

and do?

Answer 7

Gs coupled (adenylyl cyclase -> increase cAMP)

Question 8

What are the PGD2 receptors

Answer 8

DP1 and DP2

Question 9

What is the thromboxane receptor

Answer 9

TP

Question 10

What is the PGF2 receptor? and what is it coupled to?

Answer 10

FP
Gq coupled (PLC -> IP3 and Ca)

Question 11

Which EP receptor is proinflammatory and which is anti inflammatory

Answer 11

EP2 is potentially anti AND proinflammatory?!!

Question 12

Is the TP receptor pro or antiinflammatory?

Answer 12

pro-inflammatory

Question 13

What cells does EP3 activate?

Answer 13

leukocytes

Question 14

Prostaglandins sensitise ……. and cause increased pain response of ………..

Answer 14

C fibres

bradykinin

Question 15

EP1 and IP are found in ……. and knock-out of these mice have ………

Answer 15

dorsal root ganglia

no EP1 and IP = decreased pain inflammatory response

Question 16

PGs cause fever by

Answer 16

elevation of the thermoregulatory set point.

Regulated by production and action of PGE2 in the anterior hypothalamus

Question 17

What leads to a fever insensitive to NSAIDs and paracetamol?

Answer 17

cerebrovascular injection of PGE2

role of the EP3 receptor

Question 18

…………..% homology between COX 1 and 2

Answer 18

60%

Question 19

Critical residue on COX 1 and 2

Answer 19

COX-1 I-523

COX-2 V-523

Question 20

Both COX 1 and 2 are ……..dimers found on the ………………….

Answer 20

homodimers

found on the inner membrane of the ER

Question 21

2 components of the COX

Answer 21

peroxidase site

cyclooxygenase site

Question 22

How does aspirin work on cox?

Answer 22

acetylates the serine residue (530 in COX1 and 516 in COX 2)

Question 23

the COX pocket where inhibitors bind are hydrophobic or hydrophilic?
1 or 2 has more space?

Answer 23

Hydrophobic

pocket has more space on COX 2

Question 24

COX-1 produces what functions?

Answer 24

Homeostatic functions
(In GI, renal, platelet, macrophage differentiation)

Question 25

COX-2 produces what functions?

Answer 25

Inflammation

Question 26

What is the effect of Glucocorticoids on COX?

Answer 26

Inhibit COX-2

Question 27

What is the effect of growth factors on COX?

Answer 27

Stimulate COX-2

Question 28

e.g. of COX 1 selective NSAID

Answer 28

low dose asp

Question 29

e.g. of mixed COX 1 and 2 NSAID?

Answer 29

diclofenac, asp etc

Question 30

e.g. of COX-2 selective NSAID (4)

Answer 30

Meloxicam nimesulide celecoxib rofecoxib

Question 31

5 functions of PGs

Answer 31

1. labour 2. GI screstio 3. inhibit platelet aggregation (& vasodilation) 4 platelet aggregation (% vasoconstriction)

Question 32

s.e. of nonselective NSAIDS?

Answer 32

GI irritation and bleeding due to COX1 inhibition - thus reducing cytoprotective effects of PG

Question 33

s.e. rofecoxib?

Answer 33

3.9x increased incidence of thrombotic events

Question 34

Why is there an increase in thrombotic events?

Answer 34

Endothelial PGI2 derived mainly from COX-2 - suppressed No effect on platelet COX-1 therefore unbalanced PGI v TXA2 production

Question 35

Aspirin irreversibly acetylates COX so why is PGI2 still released?

Answer 35

Cells make new COX PGI is still released

Question 36

Aspirin irreversibly acetylates COX, why is TXA2 no longer released?

Answer 36

new receptors not made because TXA2 production is in anucleate platelets (days until new produced)

Question 37

Long term aspirin is also thought to help with

Answer 37

Colon and rectal cancer | AD

Question 38

Pathway for Leukotriene production?

Answer 38

AA into 5 HPETE (via 5-lipoxygenase) | into LTA2

Question 39

role of LTB4? | Receptor?

Answer 39

chemotactic | BLT receptor

Question 40

2 branches of leukotrienes made from LTA2?

Answer 40

LTB4 and LTC4 -> LTD4 -> LTE4

Question 41

receptor for LTC4 and derivatives? | 2 functions?

Answer 41

cysLT receptor 1. bronchoconstriction 2. increase vascular perm

Question 42

......... and ....... are 1000x more potent than Histamine at bronchoconstriction

Answer 42

LTC4 and LTD4

Question 43

LTC4 and LTD4 stimulate vascular ............(neutrophil independent) and LTB4 increases vascular...................... (neutrophil dependent)

Answer 43

permeability

Question 44

Chemotaxis is caused by activation of the ................. receptor

Answer 44

BLT

Question 45

Leukotrienes cause inflammation, high levels found in

Answer 45

RA synovial fluid

Question 46

``` Glucocorticoids inhibit .................... (2) and induce (1) ```

Answer 46

PLA2 (by inhibiting transcription) & COX 2 synthesis and induce endogenous PLA2 inhibitor

Question 47

5-lipoxygenase inhibitor

Answer 47

zileuton

Question 48

LTC4 and LTD4 inhibitors

Answer 48

zafirlukast | montelukast

Question 49

3 things that eicosanoids synergise with?

Answer 49

hist brady chemotaxins