Effects of dopaminergic drugs on the mast cell degranulation and nitric oxide generation in RAW 264.7 cells

Effects of dopaminergic drugs on the degranulation of mast cells (RBL-2H3 cells) and the nitric oxide production from macrophage cells (RAW 264.7) were studied. Among the dopaminergic agonists and antagonists tested, bromocriptine, 7-OH-DPAT, haloperidol, and clozapine showed potent inhibitions of mast cell degranualtion (IC50 value, 5 μM). However, these dopaminergic agents did not affect the tyrosine phosphorylations of the signaling components of the high affinity IgE receptor (FcεRI), such as Syk, PLCγ1, and PLCγ2.; This suggested that these signaling components were not involved in the inhibition of the mast cell degranulation by these compounds. On the other hand, dopamine, bromocriptine, 7-OH-DAPT, and haloperidol markedly inhibited the nitric oxide production from RAW 264.7 cells (IC50 values, 10–20 μM). Bromocriptine, a dopamine agonist that is routinely used for the treatment of Parkinsons disease, inhibited the expression of the inducible nitric oxide synthase at an early stage of the LPS-induced protein expression in a dose-dependent manner. The results suggested that these dopaminergic agents, when used for the treatment of dopamine receptors-related diseases, such as Schizophrenia or Parkinsons disease, might have additional beneficial effects.

[1]  E. Bosmans,et al.  Immunosuppressive effects of clozapine and haloperidol: enhanced production of the interleukin-1 receptor antagonist , 2000, Schizophrenia Research.

[2]  D. Lawrence,et al.  Compromised peripheral immunity of mice injected intrastriatally with six-hydroxydopamine , 2002, Journal of Neuroimmunology.

[3]  R. Fernandez-Botran,et al.  In vivo administration of l-dopa or dopamine decreases the number of splenic IFNγ-producing cells , 2003, Journal of Neuroimmunology.

[4]  W. Schmutzler,et al.  Inhibition by azelastine of the immunologically induced histamine release from isolated guinea pig mast cells. , 1981, Arzneimittel-Forschung.

[5]  Kyeong-Man Kim,et al.  Activation of Fc Epsilon RI Inhibits the Pyruvate Kinase through Direct Interaction with the Gamma–Chain , 1999, International Archives of Allergy and Immunology.

[6]  S. Ryu,et al.  Anti-allergic actions of the leaves ofCastanea crenata and isolation of an active component responsible for the inhibition of mast cell degranulation , 1999, Archives of pharmacal research.

[7]  R. Mcmurray,et al.  Bromocriptine in rheumatic and autoimmune diseases. , 2001, Seminars in arthritis and rheumatism.

[8]  K. Austen,et al.  Immunologic Release of β-Hexosaminidase and β-Glucuronidase from Purified Rat Serosal Mast Cells , 1979, The Journal of Immunology.

[9]  Y. Agid,et al.  Nitric oxide synthase and neuronal vulnerability in parkinson's disease , 1996, Neuroscience.

[10]  V. Panajotová.  The effect of dopaminergic agents on cell-mediated immune response in mice. , 1997, Physiological research.

[11]  S. Ryu,et al.  Inhibition of mast cell degranulation by tanshinones from the roots of Salvia miltiorrhiza. , 1999, Planta medica.