Prostaglandin E2 prevents diclofenac-induced enhancement of histamine release and inflammation evoked by in vivo challenge with compound 48/80 in the hamster cheek pouch.
Based on observations obtained by the use of intravital microscopy, we report that prostaglandins (PGs) can exert inhibitory effects on mast cell-dependent inflammation. Thus, the PG-synthesis inhibitors diclofenac and indomethacin potentiated extravasation of plasma evoked by challenge with the mast cell secretagogue compound 48/80. Although the plasma leakage induced by compound 48/80 was in large mediated by histamine, neither diclofenac nor indomethacin potentiated the plasma leakage caused by exogenous histamine. These findings indicated that endogenous PGs inhibited the mast cell-dependent reaction at the level of mediator release. This mode of action was confirmed, as diclofenac was found to enhance the in vivo release of histamine that ensued challenge with compound 48/80. Moreover, the enhancement of the response to compound 48/80 observed after diclofenac treatment was prevented by local administration of PGE2 (30 nM). This inhibition included both the histamine release and the plasma leakage. In addition, diclofenac enhanced the leukocyte emigration after compound 48/80 challenge, and PGE2 reversed also this effect, suggesting that endogenous PGs (e.g. PGE2) also inhibited the release of chemotactic mediators.
Raud
J
J
Department of Physiology I, Karolinska Institutet, Stockholm, Sweden.
Sydbom
A
A
Dahlén
S E
SE
Hedqvist
P
P
D000818:Animals; D002610:Cheek / Q000098:blood supply; D004008:Diclofenac / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology* / Q000627:therapeutic use; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007962:Leukocytes / Q000473:pathology; D008833:Microcirculation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D004008:Diclofenac; D003189:p-Methoxy-N-methylphenethylamine; D015232:Dinoprostone; D007213:Indomethacin