Seeman P, Niznik H B
Department of Pharmacology, University of Toronto, Ontario, Canada.
FASEB J. 1990 Jul;4(10):2737-44. doi: 10.1096/fasebj.4.10.2197154.
The loss of midbrain dopamine in Parkinson's disease is accompanied by a matching loss in the dopamine transporter and a rise in the D1 and D2 receptor densities. This is found in the brain putamen and caudate tissues from unmedicated patients, and may account for the good early clinical response to L-dopa. Long-term L-dopa treatment reverts the receptor densities toward normal levels. Positron emission tomography (PET) data and in vitro data generally concur. In schizophrenia the density of the dopamine transporter as well as that of the D1 dopamine receptor is normal. The D2 receptor density, however, is consistently elevated in postmortem brain putamen and caudate nucleus, even in tissues from neuroleptic-free or drug-naive patients. Three sets of PET and single photon emission computed tomography (SPECT) data support the postmortem findings. Early evidence indicating abnormal D2 structure as well as a reduced link between D1 and D2 warrant a detailed study of the genes for these two receptors in schizophrenia.
帕金森病中脑多巴胺的丧失伴随着多巴胺转运体的相应丧失以及D1和D2受体密度的升高。这在未接受药物治疗患者的脑壳核和尾状核组织中被发现,并且这可能解释了对左旋多巴良好的早期临床反应。长期左旋多巴治疗可使受体密度恢复到正常水平。正电子发射断层扫描(PET)数据和体外数据总体上是一致的。在精神分裂症中,多巴胺转运体以及D1多巴胺受体的密度是正常的。然而,即使在来自未使用抗精神病药物或未接受过药物治疗患者的组织中,尸检脑壳核和尾状核中的D2受体密度也持续升高。三组PET和单光子发射计算机断层扫描(SPECT)数据支持了尸检结果。早期证据表明D2结构异常以及D1和D2之间的联系减少,这使得有必要对精神分裂症中这两种受体的基因进行详细研究。