PMID- 8100641 OWN - NLM STAT- MEDLINE DCOM- 19930805 LR - 20190814 IS - 0036-5521 (Print) IS - 0036-5521 (Linking) VI - 28 IP - 6 DP - 1993 Jun TI - Effect of 5-aminosalicylic acid and analogous substances on superoxide generation and intracellular free calcium in human neutrophilic granulocytes. PG - 527-32 AB - Activated polymorphonuclear leukocytes (PMNs), which are found in the inflammatory lesions of chronic inflammatory bowel disease, produce tissue-destructive oxygen-derived free radicals. The influence of 5-aminosalicylic acid (5-ASA), its acetylated metabolite (Ac-5-ASA), sulfasalazine (SAZ), and olsalazine (OLZ) (5-ASA dimer linked by an azo group) in pharmacologically relevant concentrations (0.1-10 mM) were tested on PMN superoxide production with either the receptor-specific agent formyl-methionyl-leucyl-phenylalanine (fMLP) or the protein kinase C activator phorbol myristate acetate (PMA). Inhibition of receptor-specific superoxide production occurred at 0.07, 0.32, and 0.63 mM (IC50 values) for 5-ASA, SAZ, and OLZ, respectively. No inhibitory effects of SAZ and OLZ were observed when PMA was applied as stimulus for PMN superoxide production. The results indicate that the signal to which PMNs respond by generating superoxide is primarily due to calcium release from intracellular stores. They further suggest that SAZ and OLZ may affect the oxygen-derived free radical production in human PMNs by unspecific cytotoxicity or by interference with the nicotinamide adenine dinucleotide phosphate, reduced (NADPH) oxidase system, whereas 5-ASA itself is a free radical scavenger. FAU - Nielsen, O H AU - Nielsen OH AD - Dept. of Medical Gastroenterology C, Herlev Hospital, University of Copenhagen, Denmark. FAU - Bouchelouche, P N AU - Bouchelouche PN FAU - Berild, D AU - Berild D FAU - Ahnfelt-Ronne, I AU - Ahnfelt-Ronne I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Scand J Gastroenterol JT - Scandinavian journal of gastroenterology JID - 0060105 RN - 0 (Aminosalicylic Acids) RN - 0 (Free Radical Scavengers) RN - 0 (Free Radicals) RN - 11062-77-4 (Superoxides) RN - 3XC8GUZ6CB (Sulfasalazine) RN - 4Q81I59GXC (Mesalamine) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - 9H126Z3PF5 (N-acetyl-5-aminosalicylic acid) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - SY7Q814VUP (Calcium) RN - ULS5I8J03O (olsalazine) RN - Y5V2N1KE8U (Sulfapyridine) SB - IM MH - Aminosalicylic Acids/*pharmacology MH - Calcium/*metabolism MH - Free Radical Scavengers MH - Free Radicals MH - Humans MH - In Vitro Techniques MH - Mesalamine MH - N-Formylmethionine Leucyl-Phenylalanine/pharmacology MH - Neutrophils/*drug effects/metabolism MH - Sulfapyridine/pharmacology MH - Sulfasalazine/pharmacology MH - Superoxides/*metabolism MH - Tetradecanoylphorbol Acetate/pharmacology EDAT- 1993/06/01 00:00 MHDA- 1993/06/01 00:01 CRDT- 1993/06/01 00:00 PHST- 1993/06/01 00:00 [pubmed] PHST- 1993/06/01 00:01 [medline] PHST- 1993/06/01 00:00 [entrez] AID - 10.3109/00365529309098261 [doi] PST - ppublish SO - Scand J Gastroenterol. 1993 Jun;28(6):527-32. doi: 10.3109/00365529309098261.