PMID- 8847957 OWN - NLM STAT- MEDLINE DCOM- 19961021 LR - 20190701 IS - 0024-3205 (Print) IS - 0024-3205 (Linking) VI - 57 IP - 26 DP - 1995 Nov 17 TI - 5,6-Dihydroxyindole-2-carboxylic acid, a diffusible melanin precursor, is a potent stimulator of lipopolysaccharide-induced production of nitric oxide by J774 macrophages. PG - PL401-6 AB - Pre-incubation of J774 murine macrophages with 5,6-dihydroxyindole-2-carboxylic acid (DHICA), a diffusible intermediate in the biosynthesis of eumelanins, leads to a marked increase in the levels of nitric oxide (NO) produced by lipopolysaccharide (LPS)-induced NO-synthase (iNOS). The effect varies with DHICA concentration being maximum at a concentration of 1 x 10(-6)M, and is suppressed by the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA). No stimulation is observed when macrophages are exposed to DHICA after activation with LPS, indicating that the indole does not affect the catalytic activity of iNOS. These results point to a hitherto unrecognized role of DHICA as a chemical messenger mediating interaction between active melanocytes and macrophages in epidermal inflammatory and immune responses. FAU - D'Acquisto, F AU - D'Acquisto F AD - Department of Experimental Pharmacology, University of Naples Federico II, Italy. FAU - Carnuccio, R AU - Carnuccio R FAU - d'Ischia, M AU - d'Ischia M FAU - Misuraca, G AU - Misuraca G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Enzyme Inhibitors) RN - 0 (Indoles) RN - 0 (Lipopolysaccharides) RN - 0 (Melanins) RN - 0 (Protein Precursors) RN - 27JT06E6GR (omega-N-Methylarginine) RN - 31C4KY9ESH (Nitric Oxide) RN - 4790-08-3 (5,6-dihydroxy-2-indolylcarboxylic acid) RN - 94ZLA3W45F (Arginine) RN - EC 1.14.13.39 (Nitric Oxide Synthase) SB - IM MH - Animals MH - Arginine/analogs & derivatives/pharmacology MH - Cell Line MH - Cells, Cultured MH - Diffusion MH - Enzyme Inhibitors/pharmacology MH - Indoles/*pharmacology MH - Lipopolysaccharides/*pharmacology MH - Macrophage Activation MH - Macrophages/drug effects/*metabolism MH - Melanins/*metabolism MH - Melanocytes/metabolism MH - Mice MH - Nitric Oxide/*biosynthesis MH - Nitric Oxide Synthase/antagonists & inhibitors MH - Protein Precursors/metabolism/pharmacology MH - *Salmonella typhi MH - omega-N-Methylarginine EDAT- 1995/11/17 00:00 MHDA- 1995/11/17 00:01 CRDT- 1995/11/17 00:00 PHST- 1995/11/17 00:00 [pubmed] PHST- 1995/11/17 00:01 [medline] PHST- 1995/11/17 00:00 [entrez] AID - 0024320595022442 [pii] AID - 10.1016/0024-3205(95)02244-2 [doi] PST - ppublish SO - Life Sci. 1995 Nov 17;57(26):PL401-6. doi: 10.1016/0024-3205(95)02244-2.