PLA2 related signalling

Question 1

CHildren of PIP2 and genesis

Answer 1

Question 2

Activation

Answer 2

• Active constituitively in the cytosol. Ca2+ binding causes translocation to the membrane where its substrates exist

Question 3

Prostaglandin pathway

Answer 3

• synthesized denovo when Ca2+ is elevated
• COX1 is constituitively present in most cells
• COX2 os onduced in inflamatory cells; producing inflamatory mediators

Question 4

Prostanoids

Answer 4

• Directly synthesized by COX, an endoplasmic reticulum bound enzyme with endoperoxide and peroxidase actions

COX1: constituitive and present in most cells

COX2: induced in inflamatory cells, produces inflamation

Question 5

PIP2 PLA2 induced Signal cascade and enzymes involved

Answer 5

Question 6

Thromboxane A2

Answer 6

• Platelet aggregation
• Powerful vasoconstriction; IP3 up, DAG up cAMP up or down

Question 7

PGI2

Answer 7

Opposes platelet aggregation, Vasodilator, stimulates renin release

IPR: (cAMP, IP3, DAG) up

(cAMP) down

Question 8

Cellular events surroind inflammation

Answer 8

1. Initial dilation, some histamine release, increased vascular permeability
2. Polymorph Nuclear cells (neutrophills/eosinophills) arrive early, reactive O2 species and chemotaxins are produced
3. hours later, macrophages arrive, engulfing dead cells and bacteria generate reactive O2, NO, Eicosanoids, pyrogens etc
4. fever (maybe)

Question 9

Immune Response: generation of prostanoids

Answer 9

Splinter and bacteria enter the epithelium:

1. Tissue resident immune cells recognize bacteria and become reactive
2. Calcium is elevated, and PG’s produced via PLA2 sigalling (and NO via NOS)
3. IL1 and tumor necrosis factor promote phagocyte adhesion and attract more macrophages to the area. C5a is likely to trigger histamine release from mast cells. LOTS OF VASODILATION
4. PGE2 will also sensitize nerves resulting in increased pain

Question 10

Increase in temperature

Answer 10

Bacterial lipopolysaccharides act as pyrogens – causing the release of leukocyte pyrogens – leading to increased PGE2 synthesis in the hypothalamus – changing set-point for body’s temp regulation

Question 11

Prostaglandins and the maintenance of vascular tone

Answer 11

• TXA2 or 3 from the blood causes vasoconstriction
• Endothelilal cells produces PGI2 or PGI3 (shear stress= ca2+ up = PLA2) which causes vasodilation