Eicosanoids

Question 1

What does eicosanoids stand for?

Answer 1

20 carbon fatty acid

Question 2

How do Eicosanoids mediate their effects?

Answer 2

Agonists that work with 7-pass transmembrane receptors and heterotrimeric G-proteins

Question 3

How long is the eicosanoid half-life?

Answer 3

seconds to minutes

Question 4

What type of signaling do eicosanoids participate in?

Answer 4

Paracrine or autocrine

Question 5

Name the functions of eicosanoids

Answer 5

Platelet aggregation
Inflammation
Asthma
GI integrity
Kidney & liver homeostasis
Reproduction
Development

Question 6

What are the major classes of eicosanoids?

Answer 6

Prostacyclins
Prostaglandins
Thromboxanes
Leukotrienes

Question 7

How many unsaturated bonds does PGE2 have?

Answer 7

2

Question 8

Describe the generation of COX and 5-LOX eicosanoids

Answer 8

Phosholipase A2 cleaves a membrane phsopholipid into arachidonic acid

arachidonic acid folds and becomes either COX or LOX

Question 9

What is the major issues with Steroidal anti-inflammatory drugs?

Answer 9

Blocking the production of Phospholipase A2 can cause a loss of GI integrity due to loss of COX-1 production

Question 10

What are the latin terms for the signs of inflammation?

Answer 10

Rubor (redness)
Tumor (swelling)
Calor (fever)
Dolor (pain)

Question 11

Why does blocking COX-1 factors cause intestinal ulcers & bleeding?

Answer 11

Survival factors to prevent apoptosis of GI stem cells are produced by COX-1

Question 12

What is the main function for glucocorticoids?

Answer 12

Increase blood glucose levels for brain function

Question 13

What triggers the release of glucocorticoids?

Answer 13

Stress

Question 14

What is the pathway for the release of glucocorticoids?

Answer 14

Stress triggers release of ACTH from pituitary gland

ACTH releases glucocorticoids from adrenal gland

Question 15

What are the main actions of glucocortcoids?

Answer 15

Inhibition of glucose uptake

Catabolism of proteins

Gluconeogenesis from amino acids

Suppression of immune response

Suppression of inflammation

Question 16

What effect does COX-1 have on platelets and circulation?

Answer 16

Platelet aggregation

Vasoconstriction

Question 17

What effects does COX-2 have on platelets and circulation?

Answer 17

Platelet resting
Prevention of unwanted platelet aggregation
Vasodilation

Question 18

What is the symptom of COX-2 inhibitor toxicity?

Answer 18

Cardiovascular side effects

Unwanted platelet aggregation

Question 19

What is the advantage of low dose aspirin?

Answer 19

Blocks COX-1 without affecting COX-2 in endothelia

Question 20

Describe the activity of COX-2 in healthy endothelium

Answer 20

Endothelial cells express COX2

COX2 generates PGI2

PGI2 binds to PGI2 receptors (PI-R) to promote vasodilation and prevent platelet aggregation

PI-R signals by Gs, adenylyl cyclase, cAMP, PKA to activate Ca+ ATPase in SR to keep cytosolic Ca+ low

Low cytosolic Ca+ prevents platelets from changing shape and promotes vasodilation

Question 21

Describe activity of COX-2 in destroyed endothelium

Answer 21

Platelet adhesion to extracellular matrix stimulates COX-1

COX-1 promotes platelets to produce Thromboxane (TXA2)

TXA2 binds to thromboxane receptors (TP-R) to cause platelet activation,aggregation and vasoconstriction

TP-R signals Gq, phospholipase C, IP3 to release Ca+ from Endoplasmic reticulum

High cytosolic Ca+ initiates changes in platelet shape and promotes vasoconstriction

Question 22

What type of signaling is thromboxane and platelet aggregation?

Answer 22

Autocrine

Question 23

What ensures that TXA2 only affects a localized region?

Answer 23

Short half life of 30s

Question 24

Which eicosanoids is responsible for bronchioconstriction and muscus secretion?

Answer 24

5-LOX

Question 25

Name the 4 leukotrines that are released due to respiratory mast cell stimulation

Answer 25

LTB4, LTC4, LTD4, LTE4

Question 26

What is the function of LTB4?

Answer 26

Attracts eosinophils to leave the bloodstream and enter the airway mucosa

Question 27

What is the function of LTC4, LTD4, and LTE4?

Answer 27

Cause asthmatic symptoms:

Bronchioconstriction
Edema
Mucus secretion

Question 28

How do leukotrins LTC4, LTD4, and LTE4 cause edema?

Answer 28

Increasing vascular permeability

Question 29

How do COX inhibitors cause asthma?

Answer 29

Arachidonic acid is upregluated to form 5-LOX instead of COX1,2

Question 30

What hormones are present in the luteal phase of the cow?

Answer 30

Progesterone

PGF2alpha

Question 31

What causes the lysis of the corpus luteum?

Answer 31

PGF2alpha

Question 32

Describe the follicular cycle pathway in the cow

Answer 32

Hypothalamus secretes GnRH

GnRH stimulates pituitary gland to produce Follicle stimulating hormone & Lutenizing hormone

LH stimulates theca cells to produce androgens

FSH stimulates granulosa cells to produce estradiol

FSH stimulates inhibin production which downregulates FSH release from pituitary

Estrogen stimulates follicle growth and positive feedback on pituitary to continue producing GnRH (+ FSH, LH, Estradiol)

LH surge causes ovulation and rebuilding the follicle in to corpus luteum

Question 33

Describe what happens during the luteal phase of the cow

Answer 33

Corpus luteum synthesizes progesterone and oxytocin

Progesterone inhibits GnRH

Estradiol from maturing follicles, progesterone and oxytocin from corpus luteum stimulate PGF2alpha from non-pregnant uterus

PGF2alpha causes luteolysis

Luteolysis removes inhibitory effect of progesterone on GnRH and cow re-enters estrus

Question 34

What is Lutalyse used for?

Answer 34

Synchronization of cow estrous cycles