Lecture 18: Prostaglandins Flashcards
Inflammation
-upon infections or noxious stimuli
-eliminate harmful agents
-initiate healing process
-may injure normal tissues
Chemical mediators of inflammation
-vasoactive amines (histamine/serotonin)
-eicosanoids
-PAF
-cytokines
-complement
-coagulation and kinin
Eicosanoid types
-prostaglandins
-leukotrienes
-lipotoxins
Eicosanoids
-short lived (sec-min)
-autocrine and paracrine signaling
-bind GPCRs
Gs pathway
-generation of cAMP
-DILATION
Gq pathway
-release calcium
-CONSTRICTION
PGE2
-DILATE
-blood vessels
-bronchi
-uterus
-=O on pentagon
PGF2a
-CONSTRICTION
-blood vessels
-bronchi
-uterus
-OH on pentagon
PGI2
-DILATION of blood vessels
-INHIBITS aggregation
-L shaped
TXA2
-CONSTRICT blood vessels
-AGGREGATION
-O bridge on hexagon
Arachidonic acid
-20 carbon unsat fatty acids
-essential FAs
-most abundant
-eicosanoid precursor
phopholipase A2 (PLA2)
-release arachidonic acid from membrane phospholipids
-suppressed by corticosteroids
pathways of oxygenation of arachidonic acid
-PGH synthase (COX)
-lipoxygenase
-epoxygenase (cyt P450)
-isoprostane (free radical reaction)
PGH synthase reactions
-COX reaction
-Hydroperoxidase reaction
PGH synthase (COX) pathway
-arachadonic acid to Prostaglandins and Thromboxanes
COX reaction
-radical mediated oxidation
-arachadonic acid + 2O2 –> PGG2
-adds -OOH to C15
Hydroperoxidase reaction
-hydroperoxyl (-OOH) to hydroxyl (-OH)
-PGG2 + 2 GSH –> PGH2
Isoforms of PGH synthase
-PGH synthase I (COX-1)
-PGH synthase 2 (COX-2)
-inhibited by NSAIDs
COX-1
-expressed in various tissues
-house keeping functions
COX-2
-expressed upon stimulus in inflammatory and immune cells
-stimulated by growth factors, tumor promoters, cytokines
PGH2 can yield
-PGF2a
-PGE2
-PGI2
-TXA2
Eicosanoid Drugs
-Alprostadil
-Misoprostol
-Latanoprost
-Prostacyclin
Alprostadil
-PGE1
-RELAX smooth musc
-DILAATE vessels
-used for erectile dysfunction by inj or suppository
Misoprostol
-PGE1 derivative
-cytoprotective
-prevents peptic ulcer
-abortion in combo with mifepristone
Latanoprost
-PGF2a derivative
-topically active
-prodrug
-vasoCONSTRICTION
-used to treat glaucoma pressure
Prostacyclin
-PGI2
-vasoDILATE
-BLOCK aggregation
-treat pulmonary HTN
-IV or inhalation
-do NOT use w anticoagulants