Effects of non-steroidal anti-inflammatory drugs on isolated human polymorphonuclear leukocytes (PMN): chemotaxis, superoxide production, degranulation and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) receptor binding.
1. We have examined the effects of tolmetin and meclofenamate on isolated human PMN functions under FMLP stimulating conditions. 2. In a dose dependent manner, tolmetin and meclofenamate inhibited all PMN functions, except that tolmetin stimulated PMN chemotaxis. 3. Meclofenamate was much more potent than tolmetin as an inhibitory agent. 4. We also conducted competitive receptor binding assays for tolmetin, meclofenamate and ibuprofen on the FMLP receptor. 5. All three NSAID inhibited FMLP binding in a dose dependent manner with the potency order being meclofenamate greater than ibuprofen greater than tolmetin.
Shelly
J
J
Department of Pharmacology, University of Health Sciences, Chicago Medical School, IL 60064.
Hoff
S F
SF
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007781:Lactoferrin / Q000378:metabolism; D008469:Meclofenamic Acid / Q000494:pharmacology; D009113:Muramidase / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014046:Tolmetin / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D013481:Superoxides; D008469:Meclofenamic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D014046:Tolmetin; D007770:L-Lactate Dehydrogenase; D009113:Muramidase; D005966:Glucuronidase; D007781:Lactoferrin