Analgesic effect of mofezolac, a non-steroidal anti-inflammatory drug, against phenylquinone-induced acute pain in mice

Goto, Kazuko; Ochi, Hiroshi; Yasunaga, Yukihiro; Matsuyuki, Hirofumi; Imayoshi, Tomonori; Kusuhara, Hidenobu; Okumoto, Takeki

doi:10.1016/s0090-6980(98)00054-9

Cited by 38 publications

(26 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In spite of the presence of COX-1 in the cecum, mofezolac, a selective COX-1 inhibitor, did not exert any effects on adhesion formation, even at a dose of 30 mg/kg. This dose is thought to be sufficient for COX-1 inhibition in rodents, because mofezolac inhibits COX-1-dependent acute pain in mice, even at 10 mg/kg (Goto et al, 1998;Kusuhara et al, 1998). In a preliminary experiment, we also confirmed that platelet aggregation is inhibited upon administration of mofezolac at 30 mg/kg in mice (85.3 Ϯ 10.8% inhibition 60 min after drug administration).…”

Section: Discussionsupporting

confidence: 67%

“…Mofezolac (Mitsubishi Pharma, Tokyo, Japan) is a highly selective COX-1 inhibitor (Goto et al, 1998), and NS-398 (N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide) and CAY10404 [3-(4-methylsulphonylphenyl)-4-phenyl-5-trifluoromethylisoxazole], purchased from Cayman Chemical (Ann Arbor, MI), were used as specific COX-2 inhibitors (Habeeb et al, 2000). PGE 2 and (R)-butaprost, an analog of PGE 2 with good selectivity for the EP2 receptor subtype (Kiriyama et al, 1997), and AH6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid) and SC-19220 (8-chloro-dibenz[b,f][1,4]-oxazepine-10(11H)-carboxy-(2-acetyl)hydrazide) were also obtained from Cayman Chemical.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Significance of Cyclooxygenase-2 Induced via p38 Mitogen-Activated Protein Kinase in Mechanical Stimulus-Induced Peritoneal Adhesion in Mice

Katada

Saito²,

Ohashi³

2004

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Postoperative peritoneal adhesion represents a major complication of surgery, but the molecular mechanism underlying pathogenesis of adhesion is not fully understood. The present study investigated the roles of cyclooxygenase (COX)-1 and COX-2 in peritoneal adhesion induced by scraping the surface of the cecum and abdominal wall in mice. Slight, but macroscopically observable, peritoneal adhesion was induced even on day 1, and the extent of adhesion reached a maximum on day 7 and beyond. COX-1 mRNA was constitutively expressed in the intact cecum, and its expression level was not altered after the mechanical stimulus. In contrast, expression of the COX-2 gene was markedly increased after the stimulus, and maximum expression was observed on days 3 to 7. Mofezolac, a specific COX-1 inhibitor, had no effect on peritoneal adhesion at 30 mg/kg and had only marginal effects on prostaglandin (PG)E 2 levels in the cecum or peritoneal fluid. On the other hand, two highly selective inhibitors for COX-2, NS-398 (N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide) and CAY10404 [3-(4-methylsulphonylphenyl)-4-phenyl-5-trifluoromethylisoxazole], dose-dependently inhibited both adhesion formation and the increase in PGE 2 levels (3-30 mg/kg). The effects of NS-398 were eliminated when PGE 2 or (R)-butaprost was administered exogenously. A COX-2 antisense oligonucleotide also attenuated adhesion formation. Activation of p38 mitogen-activated protein (MAP) kinase was observed in the traumatized cecum, and an MAP kinase inhibitor, SB202190 [4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole], inhibited adhesion formation (54% inhibition at 15 M) and also reduced the COX-2 mRNA level and PGE 2 levels. In conclusion, COX-2, but not COX-1, plays a significant role in mechanical stimulus-induced peritoneal formation in the mouse cecum.

show abstract

Section: Discussionsupporting

confidence: 67%

Section: Methodsmentioning

confidence: 99%

Significance of Cyclooxygenase-2 Induced via p38 Mitogen-Activated Protein Kinase in Mechanical Stimulus-Induced Peritoneal Adhesion in Mice

Katada

Saito²,

Ohashi³

2004

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…S1P-induced cAMP accumulation was also inhibited by indomethacin, a potent inhibitor for both cyclooxygenase-1 and cyclooxygenase-2 (Fig. 4A), but not by 100 nM mofezolac, an inhibitor of cyclooxygenase-1 (Goto et al, 1998) (data not shown). The inhibition of the cAMP response by NS398 and indomethacin was not caused by the nonspecific action of the drugs, as evidenced by the finding that prostaglandin I 2 -induced cAMP accumulation was not affected by these inhibitors (Fig.…”

Section: Downloaded Frommentioning

confidence: 83%

Sphingosine 1-Phosphate Receptors Mediate the Lipid-Induced cAMP Accumulation through Cyclooxygenase-2/Prostaglandin I₂Pathway in Human Coronary Artery Smooth Muscle Cells

Damirin

Tomura

Komachi³

et al. 2004

Mol Pharmacol

View full text Add to dashboard Cite

Sphingosine 1-phosphate (S1P) has been shown to exert a variety of biological responses through extracellular specific receptors or intracellular mechanisms. In the present study, we characterized a signaling pathway of S1P-induced cAMP accumulation in human coronary artery smooth muscle cells (CASMCs). S1P induced biphasic cAMP accumulation composed of a short-term and transient response (a peak at 2.5 min) and a late and sustained response (ϳ4 -6 h). The late phase of cAMP accumulation was parallel to the increment of cyclooxygenase-2 protein expression and was inhibited by N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methane sulfonamide (NS398), a cyclooxygenase-2-specific inhibitor. We were surprised to find that the cyclooxygenase-2 inhibitor also inhibited short-term cAMP accumulation even when cyclooxygenase-2 protein expression was not yet increased. More interestingly, the short-term cAMP accumulation was also completely inhibited by pertussis toxin, an inhibitor of G i/o proteins. JTE-013, a specific antagonist for S1P 2 receptors, inhibited the S1P-induced cAMP accumulation. Furthermore, small interfering RNAs targeted for S1P 2 receptors significantly inhibited the S1P-induced cAMP accumulation. The cAMP response was also inhibited by specific inhibitors for phospholipase C, extracellular signal-regulated kinase pathways, and cytosolic phospholipase A 2 . S1P actually activated these enzyme activities and stimulated prostaglandin I 2 (PGI 2 ) synthesis. Finally, exogenously applied arachidonic acid and PGI 2 induced cAMP accumulation to a similar extent as S1P. In conclusion, S1P induced cAMP accumulation through S1P receptors, including S1P 2 receptor and G i/o protein-mediated stimulation of intracellular signaling pathways involving cyclooxygenase-2-dependent PGI 2 synthesis.

show abstract

“…COX-2-selective drugs, for example, are clinically useful in inhibiting inflammatory pain in humans (13) and are more potent than COX-1-selective NSAIDs at inhibiting pain induced by proinflammatory agents (e.g., carrageenan) in some paw inflammation assays in rodents (14,15). COX-1-selective drugs, in contrast, are superior to COX-2-selective agents at inhibiting visceronociception caused by a variety of chemical pain stimulators (16)(17)(18). Moreover, Ballou and colleagues (19) found that visceronociception was greatly decreased in COX-1 but not COX-2 knockout mice.…”

Section: Discussionmentioning

confidence: 99%

COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression

Chandrasekharan

Dai

Roos

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

1,672

1,111

View full text Add to dashboard Cite

Two cyclooxygenase isozymes, COX-1 and -2, are known to catalyze the rate-limiting step of prostaglandin synthesis and are the targets of nonsteroidal antiinflammatory drugs. Here we describe a third distinct COX isozyme, COX-3, as well as two smaller COX-1-derived proteins (partial COX-1 or PCOX-1 proteins). COX-3 and one of the PCOX-1 proteins (PCOX-1a) are made from the COX-1 gene but retain intron 1 in their mRNAs. PCOX-1 proteins additionally contain an in-frame deletion of exons 5-8 of the COX-1 mRNA. COX-3 and PCOX mRNAs are expressed in canine cerebral cortex and in lesser amounts in other tissues analyzed. In human, COX-3 mRNA is expressed as an Ϸ5.2-kb transcript and is most abundant in cerebral cortex and heart. Intron 1 is conserved in length and in sequence in mammalian COX-1 genes. 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. COX-3 and PCOX-1a are expressed efficiently in insect cells as membrane-bound proteins. The signal peptide is not cleaved from either protein and both proteins are glycosylated. COX-3, but not PCOX-1a, possesses glycosylation-dependent cyclooxygenase activity. Comparison of canine COX-3 activity with murine COX-1 and -2 demonstrates that this enzyme is selectively inhibited by analgesic/antipyretic drugs such as acetaminophen, phenacetin, antipyrine, and dipyrone, and is potently inhibited by some nonsteroidal antiinflammatory drugs. Thus, inhibition of COX-3 could represent a primary central mechanism by which these drugs decrease pain and possibly fever.A cetaminophen is often categorized as a nonsteroidal antiinflammatory drug (NSAID), even though in clinical practice and in animal models it possesses little antiinflammatory activity (1). Like NSAIDs, however, acetaminophen inhibits pain and fever and is one of the world's most popular analgesic/ antipyretic drugs. Despite acetaminophen's long use and popularity it lacks a clear mechanism of action. Flower and Vane showed that acetaminophen inhibited cyclooxygenase (COX) activity in dog brain homogenates more than in homogenates from spleen (2). This gave rise to the concept that variants of COX enzymes exist that are differentially sensitive to this drug and that acetaminophen acts centrally. Yet, even though two isozymes of COX are known, neither isozyme is sensitive to acetaminophen at therapeutic concentrations of the drug in whole cells or homogenates. Instead, COX-1 and -2 in homogenates frequently exhibit the paradoxical property of being stimulated by submillimolar concentrations of acetaminophen and inhibited by supermillimolar levels of the drug (1). This finding suggests that neither isozyme is a good candidate for the site of action of acetaminophen.In analyzing COX-1 and -2 RNA expression in dog tissues, our laboratory observed that the cerebral cortex of dog brain contains two distinct RNAs that hybridized to a canine COX-1 cDNA. ...

show abstract

Analgesic effect of mofezolac, a non-steroidal anti-inflammatory drug, against phenylquinone-induced acute pain in mice

Cited by 38 publications

References 19 publications

Significance of Cyclooxygenase-2 Induced via p38 Mitogen-Activated Protein Kinase in Mechanical Stimulus-Induced Peritoneal Adhesion in Mice

Significance of Cyclooxygenase-2 Induced via p38 Mitogen-Activated Protein Kinase in Mechanical Stimulus-Induced Peritoneal Adhesion in Mice

Sphingosine 1-Phosphate Receptors Mediate the Lipid-Induced cAMP Accumulation through Cyclooxygenase-2/Prostaglandin I₂Pathway in Human Coronary Artery Smooth Muscle Cells

COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression

Contact Info

Product

Resources

About

Analgesic effect of mofezolac, a non-steroidal anti-inflammatory drug, against phenylquinone-induced acute pain in mice

Cited by 38 publications

References 19 publications

Significance of Cyclooxygenase-2 Induced via p38 Mitogen-Activated Protein Kinase in Mechanical Stimulus-Induced Peritoneal Adhesion in Mice

Significance of Cyclooxygenase-2 Induced via p38 Mitogen-Activated Protein Kinase in Mechanical Stimulus-Induced Peritoneal Adhesion in Mice

Sphingosine 1-Phosphate Receptors Mediate the Lipid-Induced cAMP Accumulation through Cyclooxygenase-2/Prostaglandin I2Pathway in Human Coronary Artery Smooth Muscle Cells

COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression

Contact Info

Product

Resources

About

Sphingosine 1-Phosphate Receptors Mediate the Lipid-Induced cAMP Accumulation through Cyclooxygenase-2/Prostaglandin I₂Pathway in Human Coronary Artery Smooth Muscle Cells