title: Inhibitory effect of N-Acyl dopamines on IgE-mediated allergic response in RBL-2H3 cells.
abstract: Recently, endogenous N-acyl dopamines have been found to show anti-inflammatory and immunomodulatory activities. However, the effect of the N-acyl dopamines on allergic responses was not reported. In this study, we investigated whether N-acyl dopamines might inhibit immunoglobulin E-mediated degranulation in RBL-2H3 cells. When RBL-2H3 cells were exposed to palmitoyl dopamine (NP-DA), oleoyl dopamine (NO-DA) or arachidonoyl dopamine (NA-DA) at micromolar levels, all these compounds significantly inhibited the release of β-hexosaminidase, a marker of degranulation, as well as tumor necrosis factor (TNF)-α. In comparison, NP-DA, potently suppressing the release of β-hexosaminidase (IC50, 3.5 μM) and TNF-α (IC50, 2.2 μM), was more potent than NO-DA or NA-DA. Additionally, NP-DA markedly suppressed the formation of prostaglandin E2, prostaglandin D2 and leukotriene C4, corresponding to pro-inflammatory lipid mediators in asthma. In the mechanistic analyses, where the effect of NP-DA on the FcεRI cascade was examined, NP-DA significantly inhibited the phosphorylation and expression of Syk, but not Lyn. And, NP-DA also suppressed phosphorylation of ERK1/2 and Akt. Further, NP-DA decreased the phosphorylation of cPLA2 and 5-lipoxygenase (5-LO), but not cyclooxygenase-2 (COX-2). Based on these results, it is suggested that NP-DA exert anti-allergic effect on allergic response through suppressing the activation of Syk, ERK1/2, Akt, cPLA2 and 5-LO. Besides, a strong inhibition of COX-2 activity by NP-DA may be additional mechanism for its anti-allergic action. Such an anti-allergic action of N-acyl dopamines may contribute to further information about biological functions of N-acyl dopamines.
authors: Institute of Drug Research and Development, College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 305-764, Korea.
authors: Jae-Myung
authors: JM
authors: Yoo
authors: Eun Seok
authors: ES
authors: Park
authors: Mee Ree
authors: MR
authors: Kim
authors: Dai-Eun
authors: DE
authors: Sok
mesh_terms: D000215:Acylation; D000818:Animals; D018926:Anti-Allergic Agents / Q000737:chemistry* / Q000276:immunology*; D015550:Cell Degranulation; D004298:Dopamine / Q000031:analogs & derivatives* / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology; D017997:Leukotriene C4 / Q000276:immunology; D008407:Mast Cells / Q000166:cytology / Q000276:immunology; D015230:Prostaglandin D2 / Q000276:immunology; D051381:Rats; D017455:Receptors, IgE / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D001619:beta-N-Acetylhexosaminidases / Q000276:immunology
chemical_list: D018926:Anti-Allergic Agents; D018836:Inflammation Mediators; C534124:N-palmitoyl dopamine; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D017997:Leukotriene C4; D007073:Immunoglobulin E; D001619:beta-N-Acetylhexosaminidases; D015230:Prostaglandin D2; D004298:Dopamine
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