Flashcards in Eicosanoids Deck (41)
what are the 3 types of eicosanoids?
which eicosanoids are associated with inflammation?
which eicosanoid is associated with allergic reaction/hypersensitivity?
how do eicosanoids act and exert effects?
autocrine or paracrine = locally
through receptor-mediated G-protein linked signaling leading to an increase in either c-AMP or increase in intracellular Ca2+
all cells except what synthesize eicosanoids?
where does arachidonic acid reside in the cell?
C-2 posotion of membrane phospholipids
how is arachidonic acid released from phospholipids?
what structures do eicosanoids affect in inflammatory responses?
joints, skin, eyes
what do eicosanoids play an important role in?
inhibiting gastric acid secretion
regulation of BP - vasodil/vasocon
inhibit/activate platelet aggregation and thrombosis
where are eicosanoids derived from?
arachidonic acid = 20C
where are minor eicosanoids dervied from?
alpha linolenic acid obtained from diet
what is another source of arachidonic acid?
its hydrolyzed by PLA2 which removes acyl chain t 2 position
it produces arachidonic acid and leave lyso-PIP2
what is the key enzyme in eicosanoid synthesis?
cyclooxygenase (COX1 and COX2)
what does cyclooxygenase (COX1 and COX 2) do?
converts arachidonic acid to PGG2 -- PGH2
what do eicosanoid products depend on?
what is the function of COX-1?
its in most tissues
basal activity - always working constantly
produces PG and TX
what is a corticosteroid? What do they inhibit?
potent steroidal anti-inflammatory drug
inhibit the 1st step -- inhibits PLA2 so no arachidonic acid is formed
selectively inhibit COX 2
what omega family is arachidonic acid in?
What does COX-2 do?
can be induced/upregulated to become more active
what can induce COX-2?
cytokines, GF, tumor promoters, endotoxins
what inhibits the expression of COX-2?
what does induction of COX 2 lead to ?
PG synthesis = pain, heat, redness, swelling fever
how do non-steroidal anti-inflammatory drugs (NSAIDS) reduce inflammation?
inhibiting COX1 and COX 2 - reduce production of PG and TX
some selective COX2 inhibitors have been used to treat?
chronic inflammation associated with disease - celebrex
which are important to vascular health?
TXA2 and PGI2
what are platelets associated with?
what is vascular endothelium associated with?
COX 1 and COX 2
what does aspirin do ? How?
irreversibly inhibits COX 1 and COX 2 by acetylation of Serine residue in the active site!
how does low dose aspirin reduce thrombosis?
reducing platelet aggregation due to decrease TX but it doesn't reduce PGI2
platelets cannot make new COX 1 enzyme - reduced TX synthesis
endothelial cells can synthesize new COX 1 and COX 2 enzyme so they can produce what?
a diet rich in EPA leads to incorporation of what ?
20:5, omega 3 into the human phospholipid membranes
what can be used instead of arachidonic acid by PLA2 and used for eicosanoid synthesis?
what series do PG and TX formed from EPA belong to?
3 series from arachidonic acid to the 2 series
TXA3 from EPA is less what compared to TXA2 in platelet aggregation?
PGI3 and PGI2 are about the same*
what does the net effect of PGI3 and TXA3 result in?
reduction of platelet aggregation/blood clotting
how is LTA used in mast cells and eosinophils form LTC ?
addition of GSH - glutathione (tripeptide)
what are the cysteinyl-leukotrienes?
LTC, LTD, LTE
which are SRS-A and are much more potent than histamine?
how does low dose aspirin favor bettwen CV health?
reducing platelet aggregation by increasing the ratio of PGI2 to TXA2
what do you want to give a patient with asthma attack and why?
prevent relase of arachidonic acid