Methotrexate and cyclosporine treatments modify the activities of dipeptidyl peptidase IV and prolyl oligopeptidase in murine macrophages.
Analysis of the effects of cyclosporine A (25-28 mgkg(-1)) and/or methotrexate (0.1 mgkg(-1)) treatments on dipeptidyl peptidase IV (DPPIV) and prolyl oligopeptidase (POP) activities and on algesic response in two distinct status of murine macrophages (Mphis) was undertaken. In resident Mphis, DPPIV and POP were affected by neither individual nor combined treatments. In thioglycolate-elicited Mphis, methotrexate increased DPPIV (99-110%) and POP (60%), while cyclosporine inhibited POP (21%). Combined treatment with both drugs promoted a rise (51-84%) of both enzyme activities. Only cyclosporine decreased (42%) the tolerance to algesic stimulus. Methotrexate was revealed to exert prevalent action over that of cyclosporine on proinflammatory Mphi POP. The opposite effects of methotrexate and cyclosporine on POP activity might influence the availability of the nociceptive mediators bradykinin and substance P in proinflammatory Mphis. The exacerbated response to thermally induced algesia observed in cyclosporine-treated animals could be related to upregulation of those mediators.
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Laboratory of Pharmacology, Butantan Institute, 05503-900 São Paulo, Brazil.
Nascimento
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Teixeira
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Silveira
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D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism*; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D010146:Pain / Q000188:drug therapy; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases; D008727:Methotrexate