Eicosanoids Flashcards
Eicosanoids
20C FA, autocrine/paracrine signaling, short lived, rapid response
Prostaglandins - stimulus, response, target cell, receptor
PG
pyrogens stimulates receptors (IL-1/6 R)
Response: Fever
targets hypothalamus
Thromboxane (TXA) - stimulus, response, target cell, receptor
vasoconstriction, stimulates platelet aggregation,
thrombin stimulation
thrombin receptors
(blood clot),
target platelets
Leukotrienes (LT) - stimulus, response, target cell, receptor
Antigen-IgE stimulation
targets mast cells
response: anaphylatic reaction
Fc receptors
Identify the cyclooxygenase pathway in terms of the first enzyme (PGH synthase; also known as cyclooxygenase) and diagram how isomerases and reductases branch out into many derivatives.
Phospholipase A2 splits off from C2
LOX pathway - makes lipoxins –> leukotrienes
COX Pathway –> arachdonic acid –> PG or TXA
COX or PGH synthase makes COX 1/2
PGE - gastric & brain , PGD - brain, PGI - endothelial, TXA2 - platelet
Steroidal and NSAIDS
Anti-inflammatory corticosteroids (Cortisone) inhibit phospholipase A2, more potent
NSAID (aspirin) inhibit PGH synthase affecting COX pathway
COX 1 and drugs
COX 1 - Housekeeping: inhibited by baby aspirin, low dose aspirin, high dose aspirin
COX 2 and drugs
Inflammatory Response - inhibited by indomethacin (low dose), ibuprofen (high dose), 6-MNA, Celecoxib
Antagonistic effects of PGI2 and TXA2 in hemostasis/thrombosis and in regulation of blood pressure
COX inhibitor blocks TXA2 (PGI - have nucleus)
PGI2 - lining of blood vessels Gs - Increase in CAMP - Vasodilation, inhibiting platelet aggregation, NO
TXA2 - platelets - Gq - increase Ca+, release mysoin light chain - phosphorlyation - vasoconstriction, stimulating platlet aggregation, thrombin
the cytoprotective effect of PGE2 against excess stomach acidity
Regulate gastric secretion by inhibiting cAMP and HCl while stimulating HCO3, housekeeping function
the role of PGE2 in temperature regulation
Increased blood supply increases temperature, endogenous compounds that are proinflammatory, secrete endogenous pyrogens that circulate to brain and produce PGE to bind and regulate temperature, PGEs induce vasodilation and increase capillary permeability causing pain
the role of cysteinyl leukotrienes
LTA4 uses glutathione S-transferase to make leukotriene C4 into D4 then E4, slow reacting anaphylactic (LTD4 and LTE4) with antigen IgE and mast cell degranulation, increase mucous in bronchus (asthma)
