Prostaglandins Flashcards
Eicosanoids
enzyme derived products of arachadonic acid
eicosanoids catalyzed by cyclooxygenase
Prostanoids
five types of prostanoids
PGD2, PGE1/2, PGF2a, PGI2, TXA2
isoeicosanoids
free radical catalyzed products of AA
arachadonic acid (AA)
one of the fatty acids that makes up the phospholipid bilayer
phospholipase A2 (PLA2)
required for the release of AA from cell membranes
role of COX in AA pathway
converts free AA to an intermediary compound that is rapidly converted by isomerases and syntheses into prostanoids
what enzyme converts intermediate into TxA2?
thromboxane synthase (in platelets)
what enzyme converts intermediate into PGE2?
PGE2 isomerase (in GI endothelial cells)
what enzyme converts intermediate to PGI2?
PGI2 isomerase (in vascular endothelial cells)
activation of PLA2
by diverse stimuli such as inflammation, chemical, and physical stimuli
two forms of PLA2
cytosolic and inducible
cytosolic PLA2
constitutive, present in concentrations high enough for regulatory functions of the cell.
inducible PLA2
activated in setting of inflammation or cancer. responsible for greater proportion of free AA in these conditions
isoforms of COX
COX1 (constitutively) and COX2 (inducible)
expression of COX1
constitutive. but does contribute some degree of prostanoid formation during inflammation
expression of COX2
expressed in times of inflammation and cancer
function of COX1
housekeeping functions: cytoprotective in GI, platelet function
what cells only express COX1?
platelets
tissue distribution of COX1
broad distribution
what induces COX2 up regulation?
inflammatory stimuli, cytokines, growth factor, tumor promoters
COX2 is the predominant isoform in what cells?
endothelial cells
distribution of COX2
kidney, brain, synovial cells, macrophages, monocytes
what down regulates COX2
glucocorticoid
cellular mechanism of action of prostanoids
GPCR binding specific to prostaglandin activates second messenger system
catabolism of prostanoids
made quickly and degraded quickly. use as drugs is therefore limited unless made into stable analogs
what cells produce TxA2
platelets, macrophages, kidney parenchymal cells
COX isoform responsible for TxA2
COX1
TxA2 activity
induces platelet aggregation, vasoconstriction and smooth muscle cell proliferation
where is prostacyclin I2 (PGI2) produced?
endothelial cells
COX isoform for PGI2
COX2
activity of PGI2
inhibits platelet aggregation and smooth muscle cell proliferation, vasodilates, proinflammatory
role of prostaglandin E (PGE1/2)
cytoprotection in the GI by inhibition of gastric acid secretion (COX1), regulates renal blood flow via vasodilation (COX2), regulates salt via renin (COX2), induces uterine/GI smooth muscle contraction (COX1/2), cryogenic role for body temp (COX1/2), pro inflammatory effects (COX2)
role of prostaglandin F2a (PGF2a)
induces vascular smooth muscle and uterine contraction (luteal regression), vasoconstriction (COX1/2)
role of PGD2
cutaneous dilation, inhibits platelet aggregation, promotes sleep, mast cell product, chemotaxis of Th2, hair follicles
role of inflammation in prostanoid release
increases sPLA2, which increases AA release, which increases prostanoid production via increased COX2 expression
prostanoids involved in dolor
nocioception: PGE1/2, PGI2
prostanoids involved in rubor
vasodilation: PGE1/2, PGI2
prostanoids involved in calor
fever: PGE1/2
prostanoids involved in tumor
vasodilation, edema, leukocyte infiltration, chemotaxis: PGI2, PGE2, PGD
steroids
reduce the release ofAA from cell membrane by targeting PLA2
NSAIDs
reduce the production of intermediary compounds by targeting COX
Ridogrel
reduces production of TxA2 by targeting thromboxane synthase
antagonist to prostanoid
none known
carbaprost
PGF2 analog used as abortifacient, post-partum bleeding to expel placenta
misoprostol
PGE analogue used as abortifacient and for gastric cytoprotection
dinoprostone
PGE analogue used to induce labor
treatment for PDA
PGE analog
