The cyclooxygenase(COX) isoforms :COX-1is form tends to be homeostatic in functionCOX-2is induced during inflammation and tends tofacilitate the inflammatory response traumatictissue injury
The cyclooxygenase(COX) isoforms : COX-1 is form tends to be homeostatic in function COX-2 is induced during inflammation and tends to facilitate the inflammatory response traumatic tissue injury
ProstaglandinsA.role of prostaglandins as local mediatorsProstaglandins and related compounds areproduced in minute quantities by virtually alltissues.the prostaglandins do not circulate in the blood insignificant concentrationsB.synthesis ofprostaglandins
Prostaglandins A.role of prostaglandins as local mediators Prostaglandins and related compounds are produced in minute quantities by virtually all tissues. the prostaglandins do not circulate in the blood in significant concentrations. B.synthesis of prostaglandins
Biosynthetic pathway of the eicosanoidMembranephospholipidPLA2|glucocorlicoidArachidonicacid-NSAIDSCOX+5-lipoxygenaseCyclicendoperoxides5-HPETEThromboxaneProstacyclin synthetaseLTA4LTB4synthetaseLTCPGE2PGF2TXA2PGl2TD→LTEA
Biosynthetic pathway of the eicosanoid LTA4 Membrane phospholipid Arachidonic acid PLA2 COX 5-HPETE Cyclic endoperoxides PGI2 PGE2 PGF2 TXA2 glucocorlicoid LTB4 LTD4 LTC4 LTE4 NSAIDS 5-lipoxygenase
TABLE2-1.ThromboxaneProstaglandinProstaglandinProstaglandinProstacyclinPROSTANOIDLD,AIPTP,; TP,RECEPTORDP,;DP,EP,-EPFPA-FPBbrainendotheliumplateletsmast cellsuterusTARGETkidneybrainvascular smoothvascularsmoothvascular smoothORGANSmusclemusclemuscle&kidneysplateletsaiwaysairwaysmacrophagesTISSUESbrrainkidneyplateletseye
C.functions in the bodyeicosanoidActions in inflammationClassicalincreased vasodilatationprostaglandins:vascular permeabilityPGD2oedemaPGE2prostaglandins also sensitize nociceptivePGF2fibres to stimulation by otherinflammatory mediatorsThromboxane A2Platelet aggregation and vasoconstrictionProstacyclin(PGI2)Inhibition of platelet aggregation andvasodilatationLeukotrienes:IncreasevascularpermeabilityLTB4, LTC4promote leucocyle chemotaxis (and causecontractionofbronchial smoothmuscle
C.functions in the body eicosanoid Actions in inflammation Classical prostaglandins: PGD2 PGE2 PGF2 increased vasodilatation vascular permeability oedema prostaglandins also sensitize nociceptive fibres to stimulation by other inflammatory mediators Thromboxane A2 Platelet aggregation and vasoconstriction Prostacyclin(PGI2) Inhibition of platelet aggregation and vasodilatation Leukotrienes: LTB4, LTC4 Increase vascular permeability promote leucocyle chemotaxis (and cause contraction of bronchial smooth muscle)