Eicosanoids

Question 1

What are eicosanoids synthesized from? via reduction or oxidation?

Answer 1

arachidonic acid via oxidation

Question 2

What are the three classes of eicosanoids?

Answer 2

prostaglandins, thromboxanes, leukotriends

Question 3

Are Eicosanoids hydrophobic or hydrophilic? What systems are they involved in?

Answer 3

hydrophobic, involved in autocrine, paracrine, and can be endocrine

Question 4

What are eicosanoids important in?

Answer 4

inflammation

Question 5

What would you target to prevent arachidonic acid formation?

Answer 5

Phospholipase A2 or C

Question 6

What is arachodinic acid formed from?

Answer 6

The cleaving of the glycerol backbone off of diacylglercol or phospholipid

Question 7

What can arachoidonic acid be turned into? Which is more common?

Answer 7

PGH2 or Luekotriens; PGH2 is more common

Question 8

What can we target to inhibit prostaglandins?

Answer 8

PTGS1 or 2 (or cox-1 or 2)

Question 9

What can we target to inhibit leukotriends?

Answer 9

leukotriens

Question 10

What turns arachondic acid into PGH2?

Answer 10

PTGS1 or PTGS2

Question 11

What turns arachadonic acid into leukotriens?

Answer 11

LOX-5

Question 12

What the four targeted tissue for PTGS2 and what do prostaglandins do to them?

Answer 12

Joints/soft tissue - pain/inflammation;
Colon cancer - cytoprotecton and anit-apoptotic;
Uterus - luteolysis; endothelium - vasodilation and platelet resting

Question 13

What are the two targeted tissues of PTGS1 and what do prostaglandins do to them?

Answer 13

Gastric mucosa - cytoprotection and anti-apoptotic

Platelets - aggregation and vasoconstriction

Question 14

What is the targeted tissue of 5-LOX and what does it do to them?

Answer 14

airways - bronchoconstriction and mucus secretion.

Question 15

Explain the PGE2 pathway; which G proteins are involved and what occurs?

Answer 15

PGE2 binds to the E2 receptor which recruits and activates G proteins which can either activate adenyl cyclase to produce camp or inhibits adenylate cyclase . Adenylate cyclase will produce CAMP which can activate various pathways.

Question 16

Explain the TXA2 receptor pathway, what G proteins are involved, what do these G proteins activate?

Answer 16

TXA2 binds to TPb which recruit and activate Gq proteins which activate phospholipase C to produce DAG and IP3 which activate various pathways.

Question 17

What all can Eicosanoids cause? 8 things

Answer 17

Neutrophil and Eosinophil recruitment and activation
mast cell maturation
Vasodilation and leakage
SM contraction
Platelet aggregation
Enhanced epithelial barrier function
Hyperalgesia

Question 18

What are the four cardinal signs of inflammation and what are they mediated by?

Answer 18

Rubor - redness due to vasodilation
Tumor - swelling due to vascular permeability
Calor - fever due to activation of leukocytes
Dolor - pain due to increase nocipetion
Mediated by Eicosanoids

Question 19

What can glucocortecoids do to Eicosanoids and how?

Answer 19

inhibit them via Annexin A1 which inhibits phsopholipase A2

Question 20

What are the effects of Glucocorticoids?

Answer 20

Suppression of inflammation and immune response, catabolic -release AA; and liver gluconeogenesis

Question 21

What do glucocorticoids promote?

Answer 21

glucose concentration to the brain at the expense of tissues and immune response (because they both have lots of energy)

Question 22

What happens if we block PTGS1 and 2?

Answer 22

We blockPGH2 and Prostaglandins, prostacyclins, thromboxanes

Question 23

Explain what happens during cyto-protection and inflammation

Answer 23

Mild irritant in stomach > activate inflammatory pathways> arachondic acid released > in mucosa, PTGS1 > PGH2 > PGE2 activates phospholipase C > activate G1 pathway > PLC > anti-apoptotic increase mucus
Mild irritant has a 5-LOX enzyme > creates leukotriene B4

Question 24

What can inhibitors of PTGS1/2 do?

Answer 24

inhibitors reduce inflammation and relieve pain but may cause ulcers

Question 25

PTGS2 selective inhibitors do what?

Answer 25

reduce inflammation and relieve pain but may cause adverse cardiovascular events