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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
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