Download File 05

Eicosanoids
netversion
Organ-organ relationship
„local hormones”
– Histamin
– Serotonin
– Bradykinin
– Cytokines
– Eicosanoids – universal mechanism
characteristic eicosanoid profile
uptake
release
phospholipid
cleavage
PLA2
Arachidonic acid
Release
Oxygenation
reesterification
eicosanoids
phospholipids
Activation of PLA2
• by Ca2+
• by activation of the mitogen activated
protein kinase (MAPK) signalling pathway
Oxygenation of
Arachidonic acid
Cyclooxygenase
epoxygenase
(cytochrome P450)
lipoxygenase
Prostanoids
Thromboxanes
lipoxins
leukotrienes
Cyclooxygenase (COX) inhibitors
• 2 COX isozymes, COX- 1 (ubiquitous,
constitutive), COX- 2 (only in certain cells
– macrophages -, inducible)
• Non-steroid antiinflammatory drugs
(NSAID) (2006 January 88 products):
aspirin, indomethacin,diclofenac,
ibuprofen, phenylbutazone, resveratrol
• Thrombosis prevention (accepted view)
• Cancer prevention (clinical trials)
Lipoxygenases
5 lipoxygenase
neutrophil-, basophil- granulocytes,
monocytes, keratinocytes
12 lipoxygenase
platelets, pancreatic beta cells
15 lipoxygenase
reticulocytes, neutrophil-, eosinophilgranulocytes
Eicosanoids
Stimulus  sharp increase in eicosanoid
formation (50x)
No storage  release  autocrine,
paracrine functions, intracellular effects
Receptor mediated effects through G
proteins
Thromboxane receptor
Thromboxane A2 effects - signalling pathways
Module 1: Figure eicosanoids
Cell Signalling Biology
www.cellsignallingbiology.org
2007