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Prostaglandin G/H synthase 1 Prostaglandin G/H synthase 2 Prostaglandin G/H synthase 1 Nabumetone transporter 6-methoxy-2- naphthylacetic acid Transporter Prostaglandin E synthase Prostacyclin synthase Thromboxane-A synthase Cytosolic phospholipase A2 Corticosteroid 11-beta- dehydrogenase isozyme 1 Cytochrome P450 1A2 6-methoxy-2-naphthylacetic acid Nabumetone Nabumetone Nabumetone 6-methoxy-2-naphthylacetic acid 6-methoxy-2-naphthylacetic acid Prostaglandin H2 Prostaglandin E2 Prostaglandin I2 Thromboxane A2 Arachidonic acid O2 Prostaglandin G2 H2O 3-OH-nabumetone Heme Glutathione Heme Heme Phospholipids Acceptor Reduced acceptor Prostaglandin G/H synthase 2 Heme Heme Heme Heme Calcium Endoplasmic Reticulum Cytosol Blood Vessel 6-methoxy-2-naphthylacetic acid inhibits COX-1 (prostaglandin G/H synthase 1) and COX-2 (prostaglandin G/H synthase 2) on the endoplasmic reticulum membrane, preventing the conversion of arachidonic acid into PGH2. Prostaglandin H2 synthesis is reduced. COX-1 synthesizes prostaglandins necessary for normal gastrointestinal and renal function. COX-2 is responsible for prostaglandin synthesis during tissue injury and inflammation. Inhibition of COX-2 provides anti-inflammatory activity. Prostaglandin E2 is responsible for inflammation and pain by activating immune cells and stimulating pain fibres. Lower concentrations of prostaglandin E2 lowers inflammatory and pain response, hence an analgesic effect is seen. Decreasing PGE2 in the central nervous system also has an antipyretic effect. Inflamed Human Cell Blood Vessel Liver Hepatocyte
Endoplasmic Reticulum Endoplasmic Reticulum PTGS1 PTGS2 PTGS1 Unknown Unknown PTGES PTGIS TBXAS1 PLA2G4A HSD11B1 CYP1A2 6-methoxy-2- naphthylacetic acid Nabumetone Nabumetone Nabumetone 6-methoxy-2- naphthylacetic acid 6-methoxy-2- naphthylacetic acid Prostaglandin H2 Prostaglandin E2 Prostaglandin I2 Thromboxane A2 Arachidonic acid Oxygen Prostaglandin G2 Water 3-OH-nabumetone Phospholipids Acceptor Reduced acceptor PTGS2
PTGS1 PTGS2 PTGS1 PTGES PTGIS TBXAS1 PLA2G4A HSD11B1 CYP1A2 6-m-2-n Nabum Nabum Nabum 6-m-2-n 6-m-2-n PGH2 PGE2 PrstgI2 ThrmbA2 20:4 O2 PGG2 H2O 3-OH-na Heme GSH Heme Heme Phosp Accepto RA