TY - JOUR
T1 - Nimesulide, a sulfonanilide nonsteroidal anti-inflammatory drug, inhibits mediator release from human basophils and mast cells
AU - Casolaro, V.
AU - Meliota, S.
AU - Marino, O.
AU - Patella, V.
AU - De Paulis, A.
AU - Guidi, G.
AU - Marone, G.
PY - 1993
Y1 - 1993
N2 - Nimesulide (NIM) is a sulfonanilide nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of various inflammatory diseases and chemically unrelated to other acidic NSAIDs, such as acetylsalicylic acid (ASA) and indomethacin (INDO). We investigated the effects of NIM and of its in vivo metabolite, 4-hydroxy-NIM (OH-NIM), on the release of preformed (histamine) and de novo synthesized mediators (sulfidopeptide leukotriene C4 [LTC4] and prostagladin D2 [PGD2]) from human basophils and mast cells isolated from lung parenchyma (HLMC) and skin (HSMC). Histamine release from basophils challenged with rabbit anti-human IgE antibody (anti-IgE) was enhanced by preincubation with ASA or INDO (92.2 ± 7.1% at 10-3 M and 61.1 ± 6.7% at 3 x 10-6 M, respectively; P <.001). In contrast, NIM and its metabolite, OH-NIM (10-6 to 10-3 M), caused concentration-dependent inhibition (2.9 to ~60% and 3.7 to ~90%, respectively) of IgE-mediated histamine release from basophils. NIM and OH-NIM also inhibited release from basophils induced by the Ca++ ionophore A23187 and different protein kinase C activators, such as 12-O-tetradecanoyl-phorbol-13-acetate, bryostatin 1 and bryostatin 5. NIM and OH-NIM also inhibited the IgE-mediated histamine release from HLMC (52.3 ± 9.6% and 66.1 ± 12.1% at 10-3 M, respectively; P <.0001) and HSMC (67.3 ± 3.7% and 77.7 ± 12.0% at 10-3 M, respectively; P <.0001) but had little or no effect on HLMC and HSMC activated by A23187. NIM (10- 6 to 10-3 M) markedly inhibited the de novo synthesis of LTC4 from basophils, LTC4 and PGD2 from HLMC and PGD2 from HSMC. NIM and OH-NIM potentiated, whereas ASA and INDO reversed, the inhibitory effect of adenylate cyclase agonists, such as prostaglandin E1 and forskolin. In addition, NIM and OH-NIM reversed the enhancing effects of ASA and INDO on IgE-mediated histamine release from basophils.
AB - Nimesulide (NIM) is a sulfonanilide nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of various inflammatory diseases and chemically unrelated to other acidic NSAIDs, such as acetylsalicylic acid (ASA) and indomethacin (INDO). We investigated the effects of NIM and of its in vivo metabolite, 4-hydroxy-NIM (OH-NIM), on the release of preformed (histamine) and de novo synthesized mediators (sulfidopeptide leukotriene C4 [LTC4] and prostagladin D2 [PGD2]) from human basophils and mast cells isolated from lung parenchyma (HLMC) and skin (HSMC). Histamine release from basophils challenged with rabbit anti-human IgE antibody (anti-IgE) was enhanced by preincubation with ASA or INDO (92.2 ± 7.1% at 10-3 M and 61.1 ± 6.7% at 3 x 10-6 M, respectively; P <.001). In contrast, NIM and its metabolite, OH-NIM (10-6 to 10-3 M), caused concentration-dependent inhibition (2.9 to ~60% and 3.7 to ~90%, respectively) of IgE-mediated histamine release from basophils. NIM and OH-NIM also inhibited release from basophils induced by the Ca++ ionophore A23187 and different protein kinase C activators, such as 12-O-tetradecanoyl-phorbol-13-acetate, bryostatin 1 and bryostatin 5. NIM and OH-NIM also inhibited the IgE-mediated histamine release from HLMC (52.3 ± 9.6% and 66.1 ± 12.1% at 10-3 M, respectively; P <.0001) and HSMC (67.3 ± 3.7% and 77.7 ± 12.0% at 10-3 M, respectively; P <.0001) but had little or no effect on HLMC and HSMC activated by A23187. NIM (10- 6 to 10-3 M) markedly inhibited the de novo synthesis of LTC4 from basophils, LTC4 and PGD2 from HLMC and PGD2 from HSMC. NIM and OH-NIM potentiated, whereas ASA and INDO reversed, the inhibitory effect of adenylate cyclase agonists, such as prostaglandin E1 and forskolin. In addition, NIM and OH-NIM reversed the enhancing effects of ASA and INDO on IgE-mediated histamine release from basophils.
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M3 - Article
C2 - 7505332
AN - SCOPUS:0027770085
SN - 0022-3565
VL - 267
SP - 1375
EP - 1385
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 3
ER -