Term
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Definition
long chain fatty acids that act as autocrine or paracrine agents.
include:
prostaglandins, prostacyclin, thromboxanes, leukotrienes |
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Term
| What is the usual precursor of eicosanoids? |
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Definition
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Term
| Where does arachidonic acid come from? |
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Definition
| released from membrane phospholipids by phospholipase A2 |
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Term
| What is another possible substrate for eicosanoids (other than the usual arachidonic acid)? |
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Definition
| fatty acids s.a eicosapentanoic acid (found in fatty fishes), but yield different eicosanoid products |
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Term
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Definition
1) reduce cholesterol, triglycerides in recovery from acute coronary disease
2) increase tachycardia/fibrillation/cardiac death in chronic coronary disease
3) reduce Sx of inflammation in RA & psoriasis |
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Term
| What do COX1 & COX2 catalyze? |
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Definition
| 2 step reaction (oxygenation & peroxidation) => prostaglandin PGH2 formation |
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Term
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Definition
| constitutive form in stomach, platelets, & other tissue |
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Term
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Definition
1) inducible form in inflammatory tissues
2) constitutive form in kidney & vascular endothelium |
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Term
| What eicosanoid product(s) predominate in the stomach? |
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Definition
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Term
| What eicosanoid product(s) predominate in platelets? |
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Definition
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Term
| What eicosanoid product(s) predominate in vascular endothelium? |
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Definition
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Term
| How are COX products released? |
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Definition
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Term
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Definition
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Term
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Definition
| minutes (very short half lives) |
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Term
| What inactivates eicosanoids? |
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Definition
| specific enzymes by fatty acid oxidation |
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Term
| What eicosanoid products do not come from the precursor PGH2? |
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Definition
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Term
| What eicosanoid products are found in the kidney? |
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Definition
| PGE2 & PGI2
TXA2 (very little) |
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Term
| Function
PGE2 & PGI2 in kidney |
|
Definition
1) increase release of renin from juxtaglomerulat apparatus (JMA)
2) vasodilation => increase GFR
3) reduce effects of ADH in collecting duct |
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Term
| Effect
PGE2 & PGI2 in kidney |
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Definition
| increase sodium & water clearance |
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Term
| What synthesizes TXA2 during infiltration of inflammatory cells? |
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Definition
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Term
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Definition
| vasoconstriction & decline in renal function |
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Term
| What is the only vasoconstrictor eicosanoid (in humans)? |
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Definition
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Term
| What eicosanoids are produced by vascular endothelial cells? |
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Definition
| PGI2 (main source) & PGE2 (in microcirculation) |
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Term
| Effect
PGI2 & PGE2 on blood vessels |
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Definition
| vasodilation (=> hypotension & reflex tachycardia if IV injection of prostacyclin PGI2) |
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Term
Effect
prostaglandins & thromboxanes on GI smooth muscle |
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Definition
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Term
| What eicosanoids are produced by COX1 in the stomach? |
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Definition
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Term
| Function
PGE2 & PGI2 in stomach |
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Definition
| cytoprotective by maintaining secretion of mucins & limiting pepsin & acid secretion |
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Term
| What happens to GI if COX1 is inhibited? |
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Definition
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Term
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Definition
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Term
| What happens to GI if COX2 is inhibited? |
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Definition
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Term
| What is the major COX1 eicosanoid product of platelets? |
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Definition
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Term
|
Definition
1) vasoconstrictor
2) potent platelet aggregator
3) increase effects of thrombin & other aggregators |
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Term
| What can counteract TXA2 effects? |
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Definition
| 1) prostacyclin (COX2 systnesis in vascular endothelium)
2) PGD2 |
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Term
| What eicosanoids relax bronchiolar & tracheal muscle? |
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Definition
| prostacyclin (PGI2) & PGE2 |
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Term
| What eicosanoids constrict bronchiolar & tracheal muscle? |
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Definition
| TXA2 & other prostaglandins |
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Term
| What can induce PGE2 synthesis in the nervous system? |
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Definition
| pyrogenes => IL-1 induced synthesis of PGE2 |
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Term
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Definition
1) fever
2) transmission of pain fibers in SC |
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Term
| What 2 eicosanoids sensitize nerve endings of pain fibers in the periphery? |
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Definition
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Term
| What eicosanoids can cause uterine contraction? |
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Definition
| 1) TXA2
2) PGF2α
3) low doses of PGE2 |
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Term
| What effect does COX1 & COX2 inhibition have on inflammation? |
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Definition
| palliative relief from inflammation (inspite of the fact that prostaglandins & prostacyclin has anti-inflammatory effects) |
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Term
| How is PGE2 anti-inflammatory? |
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Definition
1) inhibits differentiation of B-lymphocytes into plasma cells
2) inhibits mitogen induced proliferation & lymphokine release by T lymphocytes |
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Term
| How is TXA2 pro-inflammatory? |
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Definition
1) promotes cloncal expansion of T lymphocytes
2) stimulates IL & IL receptor synthesis |
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Term
| What is the most likely explanation for the anti-inflammatory effect of COX inhibitors? |
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Definition
| diminished eicosanoid effects on vasodilation & sensitization of nociceptive nerves |
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Term
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Definition
| PGE1 used for:
1) vasodilating effect in Tx of impotence when injected directly into corpora cavernosa
2) maintain patent ductus arterosus prior to cardiac surgery |
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Term
|
Definition
| PGE11 derivative used:
1) with mifepristone in terminating pregnancies
2) for protection against peptic ulcer |
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Term
| What eicosanoids are used with oxytocin to induce labor? |
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Definition
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Term
| What eicosanoid is used to treat pulmonary & portopulmonary HTNs? |
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Definition
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Term
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Definition
| family of enzymes that can catalyze oxygenation of arachadonic acid to hyperoxides |
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Term
| Where is 5-LOX isoform found? |
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Definition
| PMNs, basophils, mast cells, eosinophils, & macrophages |
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Term
| What physiological processes are associated with 5-LOX products? |
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Definition
| asthma, anaphylactic shock, & CVD |
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Term
| What leads to the release of arachidonate & association of 5-LOX with FLAP on the nuclear membrane? |
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Definition
| activation of 5-LOX containing cells |
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Term
|
Definition
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Term
| What is arachidonate oxygenated & dehydrated by 5-LOX to produce? |
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Definition
| unstable leukotriene LTA4 |
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Term
| What happens to the unstable LTA4 produced by 5-LOX? |
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Definition
| 1) hydrated to LTB4
or
2) conjugated to LTC4 by a thiol bond to the tripeptide, glutathione |
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Term
|
Definition
| sequentially degraded by extracellular enzymes to LTD4 & LTE4 |
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Term
| Where is 12-LOX isoform found? |
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Definition
| platelets + all inflammatory cells containing 5-LOX |
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Term
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Definition
| coverts arachidonic acid directly to stereoisomers 12S-HETE & 12R-HETE |
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Term
| What happens to LTA4 when exposed to 12-LOX? |
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Definition
| coverted to lipoxins A & B |
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Term
| What shares the same receptor as LTB4? |
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Definition
| 12-HETEs (the conjugated leukotrienes bind to another class of receptors) |
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Term
| What happens to LTB4 & LTC4? |
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Definition
| actively transported out of the cell |
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Term
Duration
leukotrienes & HETEs |
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Definition
|
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Term
|
Definition
| CYP4F P450 family in leukocytes |
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Term
| Where are the conjugated leukotrienes degraded? |
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Definition
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Term
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Definition
| chemoattractant for PMNs, eosinophils, & monocytes |
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Term
|
Definition
1) attract eosinophils
2) vasoconstrict (=> depression of cornonary & myocardium blood flow)
3) increase vascular permeability (=> mucus secretion & plama exudation in airways)
4) airway: Slow Reacting Substance of Anaphylaxis (SRS-A) secreted in anaphylaxis & asthma => bronchoconstriction |
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Term
| Which leukotriene is screted by colonic epithelial cells & are therefore high in inflammatory bowel disease? |
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Definition
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Term
|
Definition
| mediate angiotensin II's release of aldosterone (not ACTH's) |
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Term
SOA
5-LOX & LT receptor antagonists |
|
Definition
asthma
(not generalized inflammation s.a. RA) |
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