Eicosanoids

Question 1

describe process of arachnoid acid formation

Answer 1

• collagen exposed
• clotting cascade releases kallikrein enzyme
• kininogen –> bradykinin
• bradykinin –> GPCR –> PA2 activation
• PA2 –> phospholipid in bilayer attacks –> arachnoid acid

Question 2

bradykinin function

Answer 2

• pain modulator = acts on sensory nerve

- vascular permeability

Question 3

what other things activate PA2

Answer 3

TNF, IL-1

Question 4

Eiconsanoids define

Answer 4

20 carbon fatty acid made from arachnoid acid this family includes prostaglandins, thromboxane, leukotrienes

Question 5

how are the prostanoids formed

Answer 5

arachnoid acid (COX enzyme acts on this)

PGG2 formed

converts to PGH2 (prostanoids synthetase act on it to make various prostanoids)

Question 6

where is TXA2, TXB2 made and function

Answer 6

-made in platelets they induce platelet aggregation + vasoconstriction + broncho-constriction

Question 7

PGI2 - where + function

Answer 7

prostacyclin made by CVS - vasodilation + inhibit platelet formation

Question 8

PGF2a where + function

Answer 8

made by macrophages + uterus cause smooth muscle contraction used to treat glaucoma increase aqueous humour outflow (latanoprost)

Question 9

PGE2

Answer 9

made by macrophages + neutrophils this is inflammatory mediator + smooth muscle contraction + acid secretion

Question 10

PGD2

Answer 10

made by mast cells increases vasodilation

Question 11

PGE2 RECEPTORS

Answer 11

EP1 receptor agonist- smooth muscle contraction e.g. dinoprostrone - used to induce abortion or labour

EP2 - Smooth muscle relaxation increases gastric fluid –> misoprostol used to block PGE2 inhibit gastric acid secretion

EP3- smooth muscle constriction decrease acid secretion + increases mucus

Question 12

PGE2 in inflammation

Answer 12

• pain modulator = sensitises sensory nerves to bradykinin
• acts on cold sensitive neurones in hypothalamus to increase body temp as WBC work better in higher body temp
• increase bone turnover + cartilage degradation in RA

Question 13

PGE metabolism

Answer 13

broken down by enzymes in lungs + kidney by oxidation

• has short half life of 1 min
• found in low conc in blood

Question 14

leukotriene production

Answer 14

arachanoid acid can be turned into leukotrienes by 5-lipoxygenase which is activated by increase in calcium

Question 15

PATHWAY TO MAKING LEUKOTRINES

Answer 15

arachnoidic acid –> 5-HPETE –> LTA4

LTA4 either forms:

• LTB4 ( high in neutrophils)
• LTC4 –> LTD4 –> LTE4 these are peptidyl leukotrienes all have polypeptide attached differ as amino acid is removed they are analphylatic substances more potent and long lasting than histamine

Question 16

lipoxins

Answer 16

anti-inflammatory mediator made from arachnoid acid

Question 17

platelet activation factor

Answer 17

causes vasodilation made by PA2