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The Pharmaceutical Society of Korea (대한약학회)
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Effects of Dopaminergic Drugs on the Mast Cell Degranulation and Nitric Oxide Generation in RAW 264.7 Cells

  • Seol, Il-Woong (Pharmacology Laboratory, College of Pharmacy, Drug Development Research Center, Chonnam National University) ;
  • Kuo, Na-Youn (Pharmacology Laboratory, College of Pharmacy, Drug Development Research Center, Chonnam National University) ;
  • Kim, Kyeong-Man (Pharmacology Laboratory, College of Pharmacy, Drug Development Research Center, Chonnam National University)
  • Published : 2004.01.01
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Abstract

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 ($IC_{50} value, 5 \mu$ M). However, these dopaminergic agents did not affect the tyrosine phosphorylations of the signaling components of the high affinity IgE receptor ($Fc\varepsilonRI$), such as Syk, $PLC\gamma1$, and $PLC\gamma2$.; 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 ($IC_{50}$ values, 10-20$\mu$M). 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.

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References

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