Eicosanoids Flashcards
What does ‘eicosa’ mean?
Twenty
What are two classical eicosanoids?
Prostanoids
Leukotrienes
What are 4 non-classical eicosanoids?
Lipoxins
Resolvins
Isoprostanes
Endocannabinoids
Under basal conditions, is synthesis or prostaglandins high or low?
Low
Name 5 prostanoid receptors
TxA2 PGD2 PGE2 PGI2 PGF2a
Where are TxA2 receptors found?
Platelets, VSMCs, macrophages, kidney
Where are PGD2 receptors found?
Mast cells, brain, airways
Where are PGE2 receptors found?
Brain, kidneys, VSMCs, platelets
Where are PGI2 receptors found?
Endothelium, VSMCs, platelets, kidney, brain
Where are PGF2a receptors found?
Uterus, airways, VSMCs, eyes
Prostaglandins act via what on target cells?
GPCRs
How many PGE2 receptors are there?
4
PGI2 receptor is Gs Gi or Gq linked?
Gs
Thromboxane receptor is Gs Gi or Gq linked?
Gq
What are the 4 functions of PGs?
Initiation of labour.
Inhibition of gastric secretion.
Inhibition of platelet aggregation and vasodilation.
Platelet aggregation and vasoconstriction.
What is PGI2 from endothelium responsible for?
Inhibition of platelet aggregation and vasodilation
What is TxA2 from platelets responsible for?
Platelet aggregation and vasoconstriction
How is EP2 potentially pro-inflammatory?
Gs/AC mediated elevation of cAMP in smooth muscle vasodilates
How is EP2 potentially anti-inflammatory?
Gs/AC mediated elevation of cAMP in leukocytes inhibits function
What does EP3 receptor do?
Activates leukocytes and mast cells.
Enhances oedema formation.
What do prostaglandins do to peripheral C-fibres?
sensitise them which increases pain response to other agents.
EP1 receptor knock out mice have increased or decreased inflammatory pain responses?
Decreased
Cerebroventricular injection of PGE2 leads to what?
Fever
What is Cox1?
Constitutive housekeeping enzyme
The products of COX1 are important in what?
Normal function of the stomach, intestine, kidney and platelets
What is COX2?
An enzyme induced in inflammation
What is COX3?
Splice variant of COX1 gene expressed in CNS
What is COX2 induced by?
TNFa
IL-1
Where are COX1 and COX 2 found?
Inner membrane of endoplasmic reticulum
What does aspirin do?
Acetylates serine residues in COX 1 and 2
What does COX2 specificity mean?
Inhibition of COX2 but not COX1 across the entire therapeutic dose range.
What are the side effects of aspirin like drugs?
Gastric irritation and bleeding, renal toxicity, bleeding
Why does aspirin cause the S/Es it does?
Due to blocking the ‘housekeeping’ COX1 and thus reducing the cytoprotective effects of PGs.
Platelet COX1 inhibition is beneficial in what?
Thrombosis
What are the 4 actions of leukotrienes?
Bronchoconstriction
Oedema
Chemotaxis
Present in inflammation
Glucocorticoids inhibit what?
PLA2
Zileuton inhibits what?
5-lipoxygenase
Zafirlukast and montelukast inhibits what?
LTC4 and LTD4
NSAIDs inhibit what?
COX
Glucocorticoids essentially inhibit what?
COX-2 synthesis
