Effects of ropivacaine on eicosanoid release from human granulocytes and endothelial cells in vitro.
OBJECTIVE
To examine the effects of ropivacaine, currently being investigated for treatment of ulcerative colitis, on the release of arachidonic acid metabolites.


METHODS
Human granulocytes and endothelial cells.


METHODS
Ropivacaine, lidocaine, hydrocortisone, 5-aminosalicylic acid or acetylsalicylic acid (10-1000 microM).


METHODS
Leukotriene B4, 5-hydroxyeicosatetraenoic acid, 6-keto PGF1 alpha and 15-hydroxyeicosatetraenoic acid were measured using immuno assays. Wilcoxon signed rank test was used for statistical calculations.


RESULTS
Ropivacaine dose-dependently inhibited zymosan-induced release of leukotriene B4 and 5-hydroxyeicosatetraenoic acid whereas the release after ionophore stimulation was not affected. Ropivacaine was more potent than 5-aminosalicylic acid but less potent compared to hydrocortisone. Ropivacaine had only a weak inhibitory effect on the release of 15-hydroxyeicosatetraenoic acid from zymosan- or ionophore-stimulated cells. In contrast to hydrocortisone and 5-aminosalicylic acid, ropivacaine only weakly affected the release of 6-keto PGF1 alpha after stimulation with thrombin.


CONCLUSIONS
The inhibited release of 5-lipoxygenase products may account for some of the anti-inflammatory effects of ropivacaine seen in the treatment of ulcerative colitis.
Martinsson
T
T
Astra Pain Control AB, Preclinical R&D, Novum Unit, Huddinge Sweden. titti.martinsson@pain.se.astra.com
Haegerstrand
A
A
Dalsgaard
C J
CJ
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002478:Cells, Cultured; D015777:Eicosanoids / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology; D019804:Mesalamine / Q000494:pharmacology; D000077212:Ropivacaine; D013917:Thrombin / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D000577:Amides; D000779:Anesthetics, Local; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D019804:Mesalamine; D015121:6-Ketoprostaglandin F1 alpha; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D000077212:Ropivacaine; D015054:Zymosan; D008012:Lidocaine; D013917:Thrombin; D001241:Aspirin; D006854:Hydrocortisone