Lecture 18: Prostaglandins

Question 1

Inflammation

Answer 1

-upon infections or noxious stimuli
-eliminate harmful agents
-initiate healing process
-may injure normal tissues

Question 2

Chemical mediators of inflammation

Answer 2

-vasoactive amines (histamine/serotonin)
-eicosanoids
-PAF
-cytokines
-complement
-coagulation and kinin

Question 3

Eicosanoid types

Answer 3

-prostaglandins
-leukotrienes
-lipotoxins

Question 4

Eicosanoids

Answer 4

-short lived (sec-min)
-autocrine and paracrine signaling
-bind GPCRs

Question 5

Gs pathway

Answer 5

-generation of cAMP
-DILATION

Question 6

Gq pathway

Answer 6

-release calcium
-CONSTRICTION

Question 7

PGE2

Answer 7

-DILATE
-blood vessels
-bronchi
-uterus

-=O on pentagon

Question 8

PGF2a

Answer 8

-CONSTRICTION
-blood vessels
-bronchi
-uterus

-OH on pentagon

Question 9

PGI2

Answer 9

-DILATION of blood vessels
-INHIBITS aggregation

-L shaped

Question 10

TXA2

Answer 10

-CONSTRICT blood vessels
-AGGREGATION

-O bridge on hexagon

Question 11

Arachidonic acid

Answer 11

-20 carbon unsat fatty acids
-essential FAs
-most abundant
-eicosanoid precursor

Question 12

phopholipase A2 (PLA2)

Answer 12

-release arachidonic acid from membrane phospholipids
-suppressed by corticosteroids

Question 13

pathways of oxygenation of arachidonic acid

Answer 13

-PGH synthase (COX)
-lipoxygenase
-epoxygenase (cyt P450)
-isoprostane (free radical reaction)

Question 14

PGH synthase reactions

Answer 14

-COX reaction
-Hydroperoxidase reaction

Question 15

PGH synthase (COX) pathway

Answer 15

-arachadonic acid to Prostaglandins and Thromboxanes

Question 16

COX reaction

Answer 16

-radical mediated oxidation
-arachadonic acid + 2O2 –> PGG2
-adds -OOH to C15

Question 17

Hydroperoxidase reaction

Answer 17

-hydroperoxyl (-OOH) to hydroxyl (-OH)
-PGG2 + 2 GSH –> PGH2

Question 18

Isoforms of PGH synthase

Answer 18

-PGH synthase I (COX-1)
-PGH synthase 2 (COX-2)
-inhibited by NSAIDs

Question 19

COX-1

Answer 19

-expressed in various tissues
-house keeping functions

Question 20

COX-2

Answer 20

-expressed upon stimulus in inflammatory and immune cells
-stimulated by growth factors, tumor promoters, cytokines

Question 21

PGH2 can yield

Answer 21

-PGF2a
-PGE2
-PGI2
-TXA2

Question 22

Eicosanoid Drugs

Answer 22

-Alprostadil
-Misoprostol
-Latanoprost
-Prostacyclin

Question 23

Alprostadil

Answer 23

-PGE1
-RELAX smooth musc
-DILAATE vessels
-used for erectile dysfunction by inj or suppository

Question 24

Misoprostol

Answer 24

-PGE1 derivative
-cytoprotective
-prevents peptic ulcer
-abortion in combo with mifepristone

Question 25

Latanoprost

Answer 25

-PGF2a derivative
-topically active
-prodrug
-vasoCONSTRICTION
-used to treat glaucoma pressure

Question 26

Prostacyclin

Answer 26

-PGI2
-vasoDILATE
-BLOCK aggregation
-treat pulmonary HTN
-IV or inhalation
-do NOT use w anticoagulants