Disease relevance of PTGS1

• Orally administered celecoxib (COX-2 inhibition) or high-dose aspirin (HDA) (COX-1 and COX-2 inhibition) did not alter time to occlusive thrombus formation compared with controls (celecoxib 77.7+/-7.2 minutes, HDA 72.0+/-18.5 minutes, control 93.0+/-21.8 minutes) [1].

High impact information on PTGS1

• In human, COX-3 mRNA is expressed as an approximately 5.2-kb transcript and is most abundant in cerebral cortex and heart [2].
• PCOX-1 proteins additionally contain an in-frame deletion of exons 5-8 of the COX-1 mRNA [2].
• This intron contains an ORF that introduces an insertion of 30-34 aa, depending on the mammalian species, into the hydrophobic signal peptide that directs COX-1 into the lumen of the endoplasmic reticulum and nuclear envelope [2].
• Intron 1 is conserved in length and in sequence in mammalian COX-1 genes [2].
• Treatment of cells with either a COX-1-selective inhibitor, SC-560, or COX-2-selective inhibitors, SC-58125 or NS-398, inhibited basal and UTP-stimulated cAMP levels [3].

Biological context of PTGS1

• Cyclooxygenase selectivity was expressed as a ratio of the concentration of an NSAID that inhibited 50% of the activity (IC50) of COX-1 to the IC50 of COX-2 [4].
• Canine clotting blood was used to test for inhibition of COX-1 activity and whole blood stimulated by lipopolysaccharide (LPS) was used to test for inhibition of COX-2 activity [5].

Anatomical context of PTGS1

• Ex vivo inhibition of cyclooxygenase product synthesis (prostaglandin E2, thromboxane B2) in whole blood was used as an indicator of activity for the constitutive COX-1 isoform, although inhibition of the synthesis of these mediators in the chamber exudate during an inflammatory process is believed to represent COX-2 inhibition [6].
• Development of these agents for veterinary use would be facilitated by the convenience of using a canine cell line as a model system to screen COX-1 and COX-2 inhibitor activities in vitro [7].
• Suppression of concentrations of PGE2 in the gastric mucosa and TXB2 in blood by aspirin administration is consistent with activity against COX-1 [8].
• PROCEDURE: COX activity was evaluated in the presence and absence of 4 NSAID (meloxicam, tolfenamic acid, carprofen, and ketoprofen), using a canine monocyte/macrophage cell line that constitutively expresses COX-1, but can be induced to express COX-2 when incubated with lipopolysaccharide [7].
• RESULT: COX-1, but not COX-2, was constitutively expressed in normal urinary bladder epithelium; however, COX-2 was expressed in neoplastic epithelium in primary tumors and in metastatic lesions of all 21 dogs and in new proliferating blood vessels in 3 dogs [9].

Associations of PTGS1 with chemical compounds

• CONCLUSIONS AND CLINICAL RELEVANCE: Meloxicam acts in vivo in dogs as a COX-1 sparing drug on target tissues by sparing gastric PGE2 synthesis while retaining antiprostaglandin effects within inflamed joints [8].
• Meloxicam, in contrast, had a minimal effect on functions mediated by COX-1 [8].
• RESULTS: Ketoprofen, aspirin, and etodolac were COX-1 selective [4].
• These data are consistent with the view that the effects of indomethacin on RBF are a consequence of inhibition of COX-1 activity [10].
• CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that carprofen and deracoxib act in vivo on target tissues as COX-1-sparing drugs by sparing gastric PGE1 and PGE2 synthesis and production of TXB2 by platelets [11].

Other interactions of PTGS1

• OBJECTIVE: To evaluate in vivo activity in dogs of meloxicam or aspirin, previously shown in vitro to be a selective cyclooxygenase-2 (COX-2) inhibitor (COX-1 sparing drug), or a nonselective COX inhibitor, respectively [8].
• Mucin assay and western blots for COX-1 and COX-2 were performed [12].

Analytical, diagnostic and therapeutic context of PTGS1

• Inhibition of prostaglandin E2 TPGE2) synthesis by each NSAID was measured by enzyme immunoassay and attributed to specific COX-1 or COX-2 activity through assessment of COX messenger RNA expression by use of northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) [7].

References