DECREASED HISTAMINE H-1 RECEPTORS IN THE FRONTAL-CORTEX OF BRAINS FROM PATIENTS WITH CHRONIC-SCHIZOPHRENIA

被引:70
作者
NAKAI, T [1 ]
KITAMURA, N [1 ]
HASHIMOTO, T [1 ]
KAJIMOTO, Y [1 ]
NISHINO, N [1 ]
MITA, T [1 ]
TANAKA, C [1 ]
机构
[1] KOBE UNIV,SCH MED,DEPT PSYCHIAT & NEUROL,KOBE 650,JAPAN
关键词
D O I
10.1016/0006-3223(91)90290-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Involvement of histamine H-1 receptor in the brains of schizophrenic patients was investigated using H-3-mepyramine as a ligand. The specific H-3-mepyramine binding in the frontal cortex was saturable with the dissociation constant (Kd) of about 0.6 nM and the maximum number of binding sites (B(max)) of 64 fmol/mg protein. Specific H-1 antagonists, mepyramine (Ki = 1.4 nM), promethazine (Ki = 1.4 nM), diphenylpyraline (Ki = 4.1 nM), triprolidine (Ki = 5.3 nM), diphenylhydramine (Ki = 35 nM), but not the specific H-2 antagonist, cimetidine (Ki > 10(5) nM), strongly inhibited the H-3-mepyramine binding. Regional distribution of the specific H-3-mepyramine binding was in the order of: frontal cortex > hippocampus > cerebellum > hypothalamus > thalamus, putamen, and pallidum. The specific H-3-mepyramine binding in schizophrenic brains was reduced by 56% in the frontal cortex. Representative Scatchard analyses of the specific H-3-mepyramine binding revealed changes resulting from a decrease in receptor density but not in receptor affinity. Down-regulation of the histamine H-1 receptor in the frontal cortex may be involved in the pathophysiology of schizophrenia.
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页码:349 / 356
页数:8
相关论文
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  • [41] DISTRIBUTION OF THE HISTAMINERGIC NEURON SYSTEM IN THE CENTRAL NERVOUS-SYSTEM OF RATS - A FLUORESCENT IMMUNOHISTOCHEMICAL ANALYSIS WITH HISTIDINE-DECARBOXYLASE AS A MARKER
    WATANABE, T
    TAGUCHI, Y
    SHIOSAKA, S
    TANAKA, J
    KUBOTA, H
    TERANO, Y
    TOHYAMA, M
    WADA, H
    [J]. BRAIN RESEARCH, 1984, 295 (01) : 13 - 25