LC 37

Question 1

What are eicosanoids?

Answer 1

signaling molecules derived from arachidonic acid

Question 2

Name a few eicosanoids

Answer 2

prostaglandins, thromboxanes and leukotrienes

Question 3

Eicosanoids are ______ which means they are usually autocrine or paracrine and are very important for __________ response

Answer 3

Hydrophobic, inflammatory

Question 4

Eicosanoid pathway

Answer 4

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

Question 5

Other names for PTGS1/PTGS2?

Answer 5

COX 1 and COX 2

Question 6

COX1 functions

Answer 6

PGE2,PGl2 for cytoprotection and anti-apoptotic is gastric mucosa
TxA2 for platelet aggregation and vasoconstriction in platelets

Question 7

COX2 functions in joints and soft tissue

Answer 7

PGE2,PGl2, PGD2, PGF2alpha

responsible for inflammation and pain

Question 8

COX2 function in colon cancer

Answer 8

PGE2 for cytoprotection and anti-apoptotic

Question 9

COX2 function in endothelium

Answer 9

PGl2 for platelet resting and vasodilation

Question 10

COX2 function in uterus

Answer 10

PGF2alpha for luteolysis

Question 11

5-LOX function in airways

Answer 11

LTB4, LTC4, LTD4, LTE4 for bronchoconstriction and mucus secretion

Question 12

Upregulation of PTGS2 eicosanoids of the joints and soft tissue results in what?

Answer 12

increased inflammation

Question 13

GPCR and eicosanoids

Answer 13

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

Question 14

Example with PGE2 receptors and two different pathways

Answer 14

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

Question 15

What are the four cardinal signs of inflammation?

Answer 15

rubor (redness), tumor (swelling), calor (fever), dolor (pain)

Question 16

SAID and inflammation overview

Answer 16

Synthetic glucocorticoids can be used to treat inflammation but they also have immune suppressive and catabolic side effects

Question 17

NSAID and inflammation overview

Answer 17

1st generation NSAIDs target COX1 and COX2 and treat pain and inflammation but cause gastric ulcers

Question 18

2nd NSAID and inflammation overview

Answer 18

2nd generation NSAIDs selectively target COX2 and treat pain and inflammation but can cause adverse cardiovascular events

Question 19

What is targeted specifically when using glucocorticoid anti-inflammation?

Answer 19

Phospholipase A2 that converts diacylglycerol/phospholipid to arachidonic acid

Question 20

Negative effect of using glucocorticoids?

Answer 20

Negatively effects your body’s natural defense response

Question 21

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

Answer 21

glucose, immune

Question 22

glucocorticoids cause _____ breakdown of tissues to release _____

Answer 22

catabolic, AA

Question 23

What is targeted specifically when using NSAIDs anti-inflammation?

Answer 23

PTGS1 and PTGS2 (COX 1 and 2)

Question 24

downside to NSAIDs

Answer 24

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

Question 25

What is targeted specifically when using COX2 anti-inflammation?

Answer 25

PTGS2 or COX2

Question 26

COX2 and platelet aggregation & vasoconstriction

Answer 26

PGl2 is stronger and
reaction leans towards platelet resting unless epithelium is broken,
then it contracts to avoid blood loss
PGl2 —> reacts w/ platelets–> pumps out [Ca]–> smooth muscle GS pathway activated to lower [Ca] to relax smooth muscle –> smooth blood flow

Question 27

Clinical correlation

Answer 27

Treating cattle with Lutalyse (exogenous PGF2alpha) triggers luteolysis and allows reentry into follicular phase so a whole herd can be treated in order to sync up cycles