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Infect & Immune 1 JAL & MW > MW L3 Eicosanoids > Flashcards

MW L3 Eicosanoids Flashcards

1
Q

Where do Eicosanoids come from?

3

A

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

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2
Q

4 Classical eicosanoids

A

prostaglandins
prostacyclins
thromboxanes
leukotrienes

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3
Q

4 non-classical eicosanoids

A

lipoxins
resolvins
isoprostanes
endocannabinoids

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4
Q

What receptor type is for prostaglandins?

A

specific GPCRs for different prostaglandins

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5
Q

What are the receptors PGE2?

A

EP1-EP2

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6
Q

What is the receptor for PGI2?

A

IP

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7
Q

EP2 and IP are couple to……

and do?

A

Gs coupled (adenylyl cyclase -> increase cAMP)

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8
Q

What are the PGD2 receptors

A

DP1 and DP2

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9
Q

What is the thromboxane receptor

A

TP

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10
Q

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

A 
FP
Gq coupled (PLC -> IP3 and Ca)
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11
Q

Which EP receptor is proinflammatory and which is anti inflammatory

A

EP2 is potentially anti AND proinflammatory?!!

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12
Q

Is the TP receptor pro or antiinflammatory?

A

pro-inflammatory

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13
Q

What cells does EP3 activate?

A

leukocytes

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14
Q

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

A

C fibres

bradykinin

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15
Q

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

A

dorsal root ganglia

no EP1 and IP = decreased pain inflammatory response

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16
Q

PGs cause fever by

A

elevation of the thermoregulatory set point.

Regulated by production and action of PGE2 in the anterior hypothalamus

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17
Q

What leads to a fever insensitive to NSAIDs and paracetamol?

A

cerebrovascular injection of PGE2

role of the EP3 receptor

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18
Q

…………..% homology between COX 1 and 2

A

60%

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19
Q

Critical residue on COX 1 and 2

A

COX-1 I-523

COX-2 V-523

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20
Q

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

A

homodimers

found on the inner membrane of the ER

21
Q

2 components of the COX

A

peroxidase site

cyclooxygenase site

22
Q

How does aspirin work on cox?

A

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

23
Q

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

A

Hydrophobic

pocket has more space on COX 2

24
Q

COX-1 produces what functions?

A 
Homeostatic functions
(In GI, renal, platelet, macrophage differentiation)
25
Q

COX-2 produces what functions?

A

Inflammation

26
Q

What is the effect of Glucocorticoids on COX?

A

Inhibit COX-2

27
Q

What is the effect of growth factors on COX?

A

Stimulate COX-2

28
Q

e.g. of COX 1 selective NSAID

A

low dose asp

29
Q

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

A

diclofenac, asp etc

30
Q

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

A

Meloxicam
nimesulide
celecoxib
rofecoxib

31
Q

5 functions of PGs

A
  1. labour
  2. GI screstio
  3. inhibit platelet aggregation (& vasodilation)
    4 platelet aggregation (% vasoconstriction)
32
Q

s.e. of nonselective NSAIDS?

A

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

33
Q

s.e. rofecoxib?

A

3.9x increased incidence of thrombotic events

34
Q

Why is there an increase in thrombotic events?

A

Endothelial PGI2 derived mainly from COX-2 - suppressed
No effect on platelet COX-1

therefore unbalanced PGI v TXA2 production

35
Q

Aspirin irreversibly acetylates COX so why is PGI2 still released?

A

Cells make new COX

PGI is still released

36
Q

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

A

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

37
Q

Long term aspirin is also thought to help with

A

Colon and rectal cancer

AD

38
Q

Pathway for Leukotriene production?

A

AA into 5 HPETE (via 5-lipoxygenase)

into LTA2

39
Q

role of LTB4?

Receptor?

A

chemotactic

BLT receptor

40
Q

2 branches of leukotrienes made from LTA2?

A

LTB4
and
LTC4 -> LTD4 -> LTE4

41
Q

receptor for LTC4 and derivatives?

2 functions?

A

cysLT receptor

  1. bronchoconstriction
  2. increase vascular perm
42
Q

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

A

LTC4 and LTD4

43
Q

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

A

permeability

44
Q

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

A

BLT

45
Q

Leukotrienes cause inflammation, high levels found in

A

RA synovial fluid

46
Q 
Glucocorticoids inhibit .................... (2)
and induce (1)
A

PLA2 (by inhibiting transcription)
& COX 2 synthesis

and induce endogenous PLA2 inhibitor

47
Q

5-lipoxygenase inhibitor

A

zileuton

48
Q

LTC4 and LTD4 inhibitors

A

zafirlukast

montelukast

49
Q

3 things that eicosanoids synergise with?

A

hist
brady
chemotaxins

Infect & Immune 1 JAL & MW (12 decks)

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