Differential effects of putative lipoxygenase inhibitors on arachidonic acid metabolism in cell-free and intact cell preparations

Inflammation ◽  
1984 ◽  
Vol 8 (2) ◽  
pp. 143-155 ◽  
Author(s):  
Joseph Chang ◽  
Maureen D. Skowronek ◽  
Mary Lou Cherney ◽  
Alan J. Lewis
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Intact Cell ◽  
Arachidonic Acid Metabolism ◽  
Lipoxygenase Inhibitors ◽  
Differential Effects

scholarly journals Effects of calmodulin and lipoxygenase inhibitors on LH (lutropin)- and LHRH (luliberin)-agonist-stimulated steroidogenesis in rat Leydig cells

1985 ◽  
Vol 232 (1) ◽  
pp. 55-59 ◽  
Author(s):  
M H Sullivan ◽  
B A Cooke
Keyword(s):  
Arachidonic Acid ◽  
Leydig Cells ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Ionophore A23187 ◽  
Lhrh Agonist ◽  
Lipoxygenase Pathway ◽  
Lipoxygenase Inhibitors ◽  
Testosterone Production

The results of this study, carried out with purified rat Leydig cells, indicate that there are no major differences in the stimulating effects of lutropin (LH) and luliberin (LHRH) agonists on steroidogenesis via mechanisms that are dependent on Ca2+. This was demonstrated by using inhibitors of calmodulin and the lipoxygenase pathways of arachidonic acid metabolism. All three calmodulin inhibitors used (calmidazolium, trifluoperazine and chlorpromazine) were shown to block LH- and LHRH-agonist-stimulated steroidogenesis. This probably occurred at the step of cholesterol transport to the mitochondria. Similarly, three lipoxygenase inhibitors (nordihydroguaiaretic acid, BW755c and benoxaprofen), inhibited both LH- and LHRH-agonist-stimulated steroidogenesis. The amounts of the inhibitors required were similar for LH- and LHRH-agonist-stimulated steroidogenesis. Steroidogenesis stimulated by the Ca2+ ionophore A23187 was also inhibited, but higher concentrations of the inhibitors were required. Indomethacin (a cyclo-oxygenase inhibitor) increased LHRH-agonist-stimulated steroidogenesis;this is consistent with the role of the products of arachidonic acid metabolism via the alternative, lipoxygenase, pathway. The potentiation of LH-stimulated testosterone production by LHRH agonist was unaffected by indomethacin or by lipoxygenase inhibitors at concentrations that inhibited LH-stimulated testosterone production by 75-100%. It was not possible to eliminate a role of calmodulin in modulating the potentiation, although higher concentrations of the inhibitors were generally required to negate the potentiation than to inhibit LH- or LHRH-agonist-stimulated testosterone production.

Differential Effects of Fexofenadine on Arachidonic Acid Metabolism in Cultured Human Monocytes

Pharmacology ◽  
2005 ◽  
Vol 76 (1) ◽  
pp. 40-45 ◽  
Author(s):  
Uwe R. Juergens ◽  
Wilfried Darlath ◽  
Meinolf Stöber ◽  
Kurt Racké ◽  
Selcuk Tasci ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Human Monocytes ◽  
Differential Effects

CYCLOOXYGENASE AND LIPOXYGENASE PRODUCTS SYNERGISTICALLY MODULATE TUMOR CELL INDUCED PLATELET AGGREGATION

1987 ◽  
Author(s):  
Bruce W Steinert ◽  
James M Onoda ◽  
Bonnie F Sloane ◽  
John D Taylor ◽  
Kenneth V Honn
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Tumor Cell ◽  
Acid Metabolism ◽  
Platelet Rich Plasma ◽  
Arachidonic Acid Metabolism ◽  
Cyclooxygenase Inhibitors ◽  
Dependent Manner ◽  
Lipoxygenase Inhibitors ◽  
Agonist Concentration

There has been considerable controversy surrounding the ability of inhibitors of arachidonic acid metabolism to concomitantly inhibit tumor cell induced platelet aggregation (TCIPA). Reconciliation of this controversy has been difficult due to the wide variability of experimental conditions (e.g., inhibitor concentration, strength of the inducing agonist).In the present study, we examined the effects of several cyclooxygenaseand lipoxygenase inhibitors on the induction of platelet aggregation by Walker 256 carcinosarcoma (W256) cells. We have previously demonstrated that aggregation of platelet rich plasma (PRP), induced by W256 cells, was initiated via a thrombin dependent mechanism. Platelet aggregation was induced by the addition of W256 cells (75,000-J500,000 cells/cuvette) to rat PRP preincubated with inhibitor(s) or diluent. The strength of the inducing stimulus affected both the degree of aggregation and the production of thromboxane A2 (TXA2) in a dose dependent manner. A weak stimulus (low concentration of W256 cells) produced only a low level of aggregation and low TXA2 production, whereas aggregation induced by a strong stimulus (high concentration of W256 cells) resulted in significant aggregation and increased TXA2 production. Preincubation (5 min., 37°C) of rat PRP with cyclooxygenase inhibitors (e.g., aspirin, indomethacin, ibuprofen) resulted in complete inhibition of platelet aggregation at low agonist concentration (75,000 W256 cells), whereas when a high agonist concentration (500,000 W256 cells) was used to induce aggregation, the inhibitors failed to inhibit TCIPA. The addition of fewer than 50,000W256 cells failed to induce any measurable platelet aggregation in the presence or absence of inhibitors. TCIPA was not affected by lipoxygenaseinhibitors (e.g.,quercetin) alone regardless of agonist concentration. Both cyclooxygenase and lipoxygenase inhibitors, however, were required to significantly inhibit TCIPA induced by high agonist concentration. Compounds which inhibited both the cycloogygenase and lipoxygenase pathways (e.g.,hydroquinone, BW755c) inhibited TCIPA at all agonist concentrations. Nafazatrom failed to inhibit TCIPA consistant with a lack of effect on platelet cyclooxygenase and lipoxygenase. Therefore, we conclude cyclooxygenase (e.g., TXA2) and lipoxygenase (e.g., 12-HETE) products of platelet arachidonic acid metabolism and the strength of the inducingagonist are important criteria in TCIPA. This study may help to clarify the current controversy regarding the inhibition of TCIPA by inhibitors of arachidonic acid metabolism.

Regulation of arachidonic acid metabolism in human amnion

1985 ◽  
Vol 110 (1_Suppla) ◽  
pp. S53-S54
Author(s):  
ST. NIESERT ◽  
M. D. MITCHELL ◽  
M. L. CASEY ◽  
P. C. MACDONALD
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Human Amnion

Arachidonic acid metabolism and insulin secretion by isolated human pancreatic islets

Diabetes ◽  
1988 ◽  
Vol 37 (7) ◽  
pp. 992-996 ◽  
Author(s):  
J. Turk ◽  
J. H. Hughes ◽  
R. A. Easom ◽  
B. A. Wolf ◽  
D. W. Scharp ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Human Pancreatic Islets
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