Flashcards in Santanam Deck (47):
Arachidonic acid is cleaved from membrane phospholipid by what
PLC - specifically cleaves phosphatidylinositides, also requires Diglyceride lipase to get to AA
what are eicosanoids
oxygenated products of polyUNsaturated FAs
What affects the function of eicosanoids
nature of the precursor fatty acids
TXA2 vs TXA3
TXA2 - vasoconstrictor
TXA3 - inactive
What is prostaglandin synthetase
Enzyme complex of:
Which COX is constitutive? Inducible?
COX-1 : Constitutive
COX-2 : Inducible
Where do you find COX-1
BV, stomach, kidney
What is COX-2 involved with?
What causes elevation of COX-2
Inflammation and cytokines
What is the effect of glucocorticoids on COX-2?
Decreased COX-2 activity
Mechanism of Action: Prostaglandins
1. Acts locally: paracrine, autocrine - short half life
2. Interacting with a receptor (GPCRs) ***
What happens after Prostaglandins bind receptor?
Inc or dec of adenylate cyclase
stimulation of phosphatidylinositol
Where is the major effect of prostaglandins seen? name the four types/areas
Smooth muscle: vascular, GI, airway, and reproductive
Which enzyme is involved with the linear pathway
Which enzyme is involved with the cyclic pathway
In the COX pathway, what is the resulting product of action of COX on AA?
Unstable endoperoxide (PGG2)
What is the action of peroxidase in COX pathway?
C15 hydroperoxide (PGG2) --> C15 hydroxyl group (PGH2)
What are the four products of COX pathway? what is the intermediate for all four?
Intermediate: PGH2 with hydroxyl group
Where is COX-2 constitutively expressed?
Brain and kidney
What does COX-1 protect against? how?
HCl via increase in stomach mucus
What is a common side effect of COX-1 inhibition?
(dec stomach mucus, more susceptible to damage due to HCl in stomach)
Effect of prostacyclin on:
- Vasodilator and Inhibit platelet aggregation
- Inhibit gastric acid secretion, increased mucus secretion
- Relaxes uterine muscle
- Induces pain
Effect of Prostaglandin on:
Vascular, Airway, GI, pain: same as prostacyclin
CONTRACTS uterine smooth muscle - low conc
relaxes in high conc
What is the effect of prostaglandins on fever?
Direct pyrogen in hypothalamus
What cytokine stimulates PGE2?
Effect of Thromboxane on:
- Vasoconstrictor and stimulates Platelet aggregation
- Uterine contraction
What is major product of platelet COX-1? COX-2?
Effect of Prostaglandin F2a on:
- Contracts uterine muscle
What effect does PGF2a have on the eye?
Decreases intraocular pressure
What is PGF2a used to treat? What is defective in this disease?
loss of COX-2
What keeps DA open in fetus?
PGE2/1 and PGI2
What happens to DA after birth?
Closes because of decreased PGE2/1, PGI2
What is used to keep DA open in cyanotic heart disease?
Alprostadil via IV infusion
What is used to close DA?
What specific enzyme is used in the lipoxygenase pathway?
What is the intermediate in LOX pathway?
Name two chemotactic agents for PMN, Eosinophils, monocytes formed in the linear pathway
What does LTE4 (LTC4, LTD4) do?
Inc vascular permeability
Components of slow reacting substance of anaphylaxis
What are LTE4, LTC4, LTD4 known as
What is the side group on 5-HETE and what is it converted to by ______ to LTA4?
5-hydroperoxide to 5,6-epoxide by Dehydrase
What enzyme converts LTA4 to Cysteinyl leukotrienes
What enzyme converts LTA4 to LTB4?
What is the LOX pathway associated with?
Asthma, anaphylactic shock, CVD
Which leukotriene produces hyperalgesia
Which leukotrienes are chemoattractants for eosinophils?
What is FLAP?
5-LOX activated protein