Prostaglandins and Leukotrienes Flashcards
Eicosanoids
Oxygenation products of arachidonic acid consisting or prostanoids and leukotrienes
Phospholipase A2
Upon inflammatory/mitogenic signals, goes into membrane and cleaves AA off phospholipid
Biosynthesis of Prostanoids
COX Cleaves AA into unstable PGG2 then PGH2, which is quickly converted to TXA2 (if platelet) or PGI2 (if endothelium)
Difference b/w COX1 and 2
COX1 is housekeeping, always active
COX2 is inducible form associated w/ inflammation/cytokines
2 Drugs that Inhibit Synthesis of Prostanoids (& targets)
Corticosteroids - PLA2
NSAIDs - COX
Biosynth of Leukotrienes
5-LOX w/ FLAP convert AA to intermediates then either the cysteinyl leukotrienes (LTC4, LTD4, LTE4) or LTB4
3 Kinds of Drugs that Inhibit Synth of Leukotrienes
Corticosteroids - PLA2 inhibitor
5-LOX Inhibitors
FLAP Inhibitor
TXA2 Mechanism
Created by COX1 and released, acts on TP GPCR auto or paracrine, activates Gq, activates PLC, increases Ca, causes response including PLA2 activation for amplified response
2 Responses of TXA2 (in 2 diff cell types)
Promotes aggregation of shit in platelets
Promotes vasoconstriction in vascular smooth muscle
PGI2 (Prostacyclin) Mechanism
Created by COX2 and released, acts on IP GPCR auto or para, activates Gs, activates AC which increases cAMP, and causes effects antagonistic to TXA2
2 Effects of PGI2 (in 2 diff cell types)
Inhibit platelet aggregation
VSM Relaxation
3 Inflammatory Effects of PGE2 in 3 Locations
Inflammatory Response: induced by COX2 to increase vascular permeability (edema) and enhance leukocyte infiltration
CNS: COX to Induce fever
PNS: COX to sensitize peripheral nerves to painful stimuli
Effects of 3 Leukotrienes
LTB4 - chemoattractant
LTC4 - bronchoconstrictor
LTD4 - slow acting substance of anaphylaxis
Mech of LTC4
Released, acts on CysLT2 GPCR either auto or paracrine, activates Gq, PLC, then increases Ca, causing bronchial smooth muscle contraction
