Experimental Study on the Expression of Striatal Dopamine Receptors in the Rat Model of Parkinsonism

파킨슨씨병 모델 흰쥐에서 줄무늬체 도파민 수용체의 발현에 대한 연구

  • Oh, Chang-Wan (Department of Neurosurgery, Seoul National University, College of Medicine) ;
  • Han, Dae Hee (Department of Neurosurgery, Seoul National University, College of Medicine) ;
  • Chung, Chun Kee (Department of Neurosurgery, Seoul National University, College of Medicine) ;
  • Cho, Sa-Sun (Department of Anatomy, Seoul National University, College of Medicine) ;
  • Park, Kyeong-Han (Department of Anatomy, Seoul National University, College of Medicine) ;
  • Kim, Yong-Sik (Department of Pharmacology, Seoul National University, College of Medicine) ;
  • Park, Chan-Woong (Department of Pharmacology, Seoul National University, College of Medicine)
  • 오창완 (서울대학교 의과대학 신경외과학교실) ;
  • 한대희 (서울대학교 의과대학 신경외과학교실) ;
  • 정천기 (서울대학교 의과대학 신경외과학교실) ;
  • 조사선 (서울대학교 의과대학 해부학교실) ;
  • 박경한 (서울대학교 의과대학 해부학교실) ;
  • 김용식 (서울대학교 의과대학 약리학교실) ;
  • 박찬웅 (서울대학교 의과대학 약리학교실)
  • Received : 1998.09.01
  • Accepted : 1998.10.26
  • Published : 2000.02.28

Abstract

This study was designed to investigate the underlying mechanisms for the temporal changes of the striatal dopamine D2 receptors in the rat model of parkinsonism. After injection of the 6-hydroxydopamine into the substantia nigra of adult rats, we measured the receptor binding capacity(Bmax), mRNA and protein of the D2 receptor at 2, 4 and 8 weeks. Following the lesion, mRNA and protein were elevated simultaneously on both sides of the striata. They showed more increase on the normal side at 2 and 4 weeks, and then they were almost equally abundant on both sides at 8 weeks. We also observed their increased production in the diffuse cortical and subcortical regions. The Bmax value also increased bilaterally in both striata, and was higher on the normal side at 2 weeks and then on the lesioned side at 4 and 8 weeks. These findings suggest that production of the striatal D2 receptor is regulated at the transcriptional level in this animal model. They also imply that this control may be mediated through a pathway which can have influence on the whole brain, rather than the local control of the dopamine content alone. The measured functional activity(Bmax) of the D2 receptor was not proportional to the amount of the receptor mRNA and proteins produced. This difference may be explained by the post-translational modification of the receptor proteins, which may be controlled by such factor as the local concentration of dopamine.

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