MBOD--Eicosanoids Flashcards
COX 1
cyclooxygenase; homesotatic protection and maintenance functions, expressed via constitutive expression
COX 2
functional role in pro-inflammatory and mitogenic effects; induced by TNFalpha, LPS, IL-1 and 2, EGF, and IFN gamma
In what path do cycloxygenases function?
in the PG synthesis pathways
Three pathways in which ArA is a substrate?
cycloxygenase
lipoxygenase
epoxidation (CYP450)
What are the 3 products of the lipoxygenase pathway?
leukotrienes
lipoxins
HETE
What is the major intermediate of the lipoxygenase pathway?
HPETE
What inhibits the lipoxygenase pathway?
synthesis inhibitors in asthma drugs
What inhibits the COX pathways?
NSAIDs (like ASA)
What are physiologic functions of eicosanoids?
paracrine signalers for vasoregulation, inflammation, bronchoregulation
Through what GPCR pathway do PGs E/D/I function?
Gs, so they activate adenylyl cyclase and increase cAMP/PKA/cell changes
Through what GPCR pathway do PGF2, TXA2, and leukotrienes function?
Gq: so they cleave PIP2 and IP3 releases Ca2+ from ER
What induces the release of eicosanoids?
cytokines and other hormone signals
What is the precursor for eicosanoid synthesis?
arachidonic acid, produced from phospholipids
What kinds of PGs do endothelial cells produce?
PG I/E/D to inhibit platelet aggregation
What catalyzes the formation of epoxides?
CYP 450
What enzyme catalyzes the formation of PGs and what is the major intermediate?
prostaglandin synthase; PGH2/PGG2
What are the two catalytic functions of PG synthase and what do they each produce?
cycloxygenase–PGG2
peroxidase–PGH2
What enzyme catalyzes the formation of leukotrienes, HETE, and lipoxins?
lipoxygenase
What enzymes produce ArA?
PLA2 and DG lipase, from phospholipids and DAG respectively
Where does glutathione come in with PG synthesis?
it is needed to help out the peroxidase function of PGS to convert PGH2–>PGG2
What are the common structural features of PGs?
20 Carbons; 5-C ring (C8-12); 2 chains with 8 and 7 Cs each; substituent at C9 and C11; hydroxyl at C15; up 2 two double bonds in hydrocarbon chain
What is the main physiological function of thromboxanes?
platelet aggregation and vasoconstriction; released at wounds
What inhibits phospholipases?
Corticosteroids
What is the basis of endometriosis?
estrogen tells the endometrium to grow and that causes pain and infertility; PGE2 stimulated estrogen production, both induce COX-2 so COX inhibitors like NSAIDs will help alleviate pain
What is the effect of PGE on neurotransmission?
inhibits Epi release in sympathetic nerves, increase peripheral nerves’ sensitization
What kind of activity does Acetaminophen have?
CNS anelgesic activity
What is the effect of PGE in bones?
increases bone turnover, absorption, and formation
What is the normal action of TXA2 on platelets, and what is the effect of inhibiting COX on TXA2?
normally TXA2 will promote platelet aggregation and vasoconstriction, but inhibiting it will decrease platelet aggregation and inhibit vasoconstriction; this can affect the healing process
What is the problem with selective COX-1 or COX-2 inhibitors?
COX-1 will inhibit platelet aggregation, leading to GI ulcerations and poor healing; inhibiting COX-2 will prevent platelet inhibition and raise risk of clot formation
What is the effect of PGs in the kidney?
COX-1 derived will promote sal excretion
COX-2 derived will maintain regular kidney filtration
What is the role of PGE in fevers?
it is involved in making a fever, so NNAs lower fever by inhibiting COX path/PGE
Epoxides play a role in…
vascular and myogenic tone
Eicosatrienoic products think…
vasodilation
Hydroxyeicosatetreonoic products think…
vascular and kidney effects that implicate it in hypertension
Give example uses of exogenous PGE/PGF2alpha
- induce labor/uterine contraction
- ED
- Pulmonary HTN
- patent ductus arteriosis
