Disease relevance of COX2

• Prostaglandin E(2) (PGE(2)) and nitric oxide (NO), derived from the enzymes cyclo-oxygenase 2 (COX2) and NO synthase 2 (NOS2), are inflammatory mediators that modulate numerous physiological and pathophysiological processes and are potentially important pharmacological targets in osteoarthritis [1].

High impact information on COX2

• METHODS: Newborn pigs were treated intravenously every 8 hours for 48 hours with saline, 40 mg/kg nonselective COX inhibitor ibuprofen, 80 mg/kg COX-1 inhibitor valeryl salicylate, or 5 mg/kg DuP697 and 5 mg/kg NS398, COX-2 inhibitors [2].
• PURPOSE: To determine the relative contribution of cyclooxygenase (COX)-1 and COX-2 in regulating prostaglandin (PG) E2 and PGF2alpha receptors (EP and FP, respectively) densities and their functions in retinal vasculature of neonatal pigs [2].
• Retinal vessel EP1, EP3, and FP receptor densities increased approximately threefold after treatments with COX-1 or COX-2 inhibitors, and five- to sixfold after ibuprofen treatment [2].
• In normal guinea pigs, SC-560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole] (COX-1 inhibitor) or DFU [5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone] (COX-2 inhibitor) significantly increased the contractile response to histamine, these effects being not additive [3].
• A COX-2-dependent release of prostacyclin (PGI(2)), but not prostaglandin E(2), was observed in tracheal tissues from normal and OVA-sensitized guinea pigs [3].

Biological context of COX2

• In contrast to COX-1, a positive immunostaining reaction for COX-2 was detected only on days 12-16 after ovulation and on days 14-16 of pregnancy [4].
• COX-2 rather than COX-1 seems to be the primary enzyme responsible for modulated PGs production at the time of luteolysis in cyclic and during implantation in pregnant animals [4].
• We studied the effect of selective COX-2 inhibition on left ventricular remodeling and function after MI in a pig model [5].

Anatomical context of COX2

• Immunohistochemistry showed that COX-1 and COX-2 are constitutively present in normal guinea pig trachea, particularly in the epithelial layer, and that COX-2 expression is enhanced in OVA-sensitized animals both in epithelial and subepithelial tissues [3].
• CONCLUSION: Mechanical compression of articular cartilage increased COX2 and PGE(2) production through a NO-dependent pathway, and therefore pharmacological agents that target the NOS2 pathway in cartilage may have a significant influence on prostanoid production in the joint [1].
• In conclusion, these results indicate specific patterns of COX-1 and COX-2 expression in the porcine endometrium throughout the oestrous cycle and early pregnancy [4].
• COX-1 and COX-2 were localized in the luminal and glandular epithelium as well as in the uterine stroma [4].

Associations of COX2 with chemical compounds

• We proceeded to establish direct evidence that COX-2-generated prostaglandins govern PGE2 and PGF2alpha receptor density and function in the cerebral vasculature of the newborn [6].
• METHODS AND RESULTS: Twenty-two pigs were assigned to COX-2 inhibition with a COX-2 inhibitor (COX-2i; celecoxib 400 mg twice daily; n=14) or a control group (n=8) [5].
• Hence, we determined PGE2 and PGF2alpha receptor density and functions in brain vasculature by using newborn pigs treated with saline, ibuprofen, COX-1 inhibitor (valerylsalicylate), or COX-2 inhibitors (DUP-697 and NS-398) [6].

Other interactions of COX2

• NOS inhibition by l-N(G)-nitro-arginine methyl ester (l-NAME) did not affect histamine-induced contraction but reversed the increase caused by COX-1 blockade while not modifying the enhancement associated with COX-2 inhibition [3].

References