LC 37 Flashcards
What are eicosanoids?
signaling molecules derived from arachidonic acid
Name a few eicosanoids
prostaglandins, thromboxanes and leukotrienes
Eicosanoids are ______ which means they are usually autocrine or paracrine and are very important for __________ response
Hydrophobic, inflammatory
Eicosanoid pathway
Both start at diacylglycerol/phospholipid and are converted to arachidonic acid via Phospholipase (A2 or C)
Pathway 1: –(PTGS1/PTGS2)–>PGH2–>prostaglandins, thromboxanes, prostacycins
Pathway 2: –(5-LOX)–>5-hydroperoxy-eicostetraeoic acid–>Leukotrienes
Other names for PTGS1/PTGS2?
COX 1 and COX 2
COX1 functions
PGE2,PGl2 for cytoprotection and anti-apoptotic is gastric mucosa
TxA2 for platelet aggregation and vasoconstriction in platelets
COX2 functions in joints and soft tissue
PGE2,PGl2, PGD2, PGF2alpha
responsible for inflammation and pain
COX2 function in colon cancer
PGE2 for cytoprotection and anti-apoptotic
COX2 function in endothelium
PGl2 for platelet resting and vasodilation
COX2 function in uterus
PGF2alpha for luteolysis
5-LOX function in airways
LTB4, LTC4, LTD4, LTE4 for bronchoconstriction and mucus secretion
Upregulation of PTGS2 eicosanoids of the joints and soft tissue results in what?
increased inflammation
GPCR and eicosanoids
Different receptors are found in different tissues for different effects but can be found in the same cells. Point of regulation. Ex. can be stimulatory down one pathway but inhibitory down another
Example with PGE2 receptors and two different pathways
Pathway 1: PGE2 binds EP2 receptor–>EP2 recruits Gs–>Ga,s activates adenylate cyclase–>cAMP–>pathways activated
Pathway 2: PGE2 binds EP1 receptor–>EP1 recruits Gi–>Ga,i inhibits adenylate cyclase–>cAMP is not made
What are the four cardinal signs of inflammation?
rubor (redness), tumor (swelling), calor (fever), dolor (pain)
SAID and inflammation overview
Synthetic glucocorticoids can be used to treat inflammation but they also have immune suppressive and catabolic side effects
NSAID and inflammation overview
1st generation NSAIDs target COX1 and COX2 and treat pain and inflammation but cause gastric ulcers
2nd NSAID and inflammation overview
2nd generation NSAIDs selectively target COX2 and treat pain and inflammation but can cause adverse cardiovascular events
What is targeted specifically when using glucocorticoid anti-inflammation?
Phospholipase A2 that converts diacylglycerol/phospholipid to arachidonic acid
Negative effect of using glucocorticoids?
Negatively effects your body’s natural defense response
1st generation NSAIDs target COX1 and COX2 and treat pain and inflammation but cause gastric ulcers promote ______ concentration to the brain at the expense of tissues and ______ response
glucose, immune
glucocorticoids cause _____ breakdown of tissues to release _____
catabolic, AA
What is targeted specifically when using NSAIDs anti-inflammation?
PTGS1 and PTGS2 (COX 1 and 2)
downside to NSAIDs
NSAID will cut off the pathway that would usually tell the cells in increase mucus and the signals that tell epithelium that it will good okay. Now no protective and insults only–>epithelium apoptosis, sheds and leads to gastric ulcers, oxidative damage, increase HCL
