Effects of lysine clonixinate on cyclooxygenase I and II in rat lung and stomach preparations.
Lysine clonixinate (LC) is a drug of antiinflammatory antipyretic and analgesic activity that produces minor digestive side-effects. This fact induced us to think that LC is possibly a weak COX-1 inhibitor. In order to investigate our hypothesis we inhibited cyclooxygenase activity with LC or indomethacin (INDO) in rat lung and stomach obtained from rats treated with lipopolysacharide (LPS) and control rats. Rat lung preparations incubated with 14C-arachidonic acid synthesise mainly PGE2. LC at 2.5 and 4.1 x 10(-5) M does not modify the basal production of PGE2 (probably COX-1) but at 6.8 x 10(-5) M significantly inhibited PGE2 production (approximately 48.5% inhibition, P<0.001). On the other hand, INDO at 10(-6) inhibited the basal production of PGE2 by around 73%. In LPS-treated rats, the production of PGE2 was significantly higher than in the lungs of control rats, probably due to the induction of COX-2. The addition of LC at 2.7 and 4.1 x 10(-5) M recovered the control values of PGE2 inhibiting, probably only from COX-2 activity. LC at higher concentrations (6.8 x 10(-5) M) and INDO 10(-6) M inhibited PGE2 formed by COX-2 and also partly by COX-1 activity.
Franchi
A M
AM
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Di Girolamo
G
G
de los Santos
A R
AR
Martí
M L
ML
Gimeno
M A
MA
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D003002:Clonixin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000201:enzymology*; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects* / Q000201:enzymology*; D013929:Thromboxane B2 / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; C089163:lysine clonixinate; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D008239:Lysine; D015232:Dinoprostone; D003002:Clonixin; D007213:Indomethacin