Decreased histamine H1 receptors in the frontal cortex of brains from patients with chronic schizophrenia.
Involvement of histamine H1 receptor in the brains of schizophrenic patients was investigated using 3H-mepyramine as a ligand. The specific 3H-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 (Bmax) of 64 fmol/mg protein. Specific H1 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 H2 antagonist, cimetidine (Ki greater than 10(5) nM), strongly inhibited the 3H-mepyramine binding. Regional distribution of the specific 3H-mepyramine binding was in the order of: frontal cortex greater than hippocampus greater than cerebellum greater than hypothalamus greater than thalamus, putamen, and pallidum. The specific 3H-mepyramine binding in schizophrenic brains was reduced by 56% in the frontal cortex. Representative Scatchard analyses of the specific 3H-mepyramine binding revealed changes resulting from a decrease in receptor density but not in receptor affinity. Down-regulation of the histamine H1 receptor in the frontal cortex may be involved in the pathophysiology of schizophrenia.
Nakai
T
T
Department of Pharmacology, Kobe University School of Medicine, Japan.
Kitamura
N
N
Hashimoto
T
T
Kajimoto
Y
Y
Nishino
N
N
Mita
T
T
Tanaka
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011738:Pyrilamine / Q000378:metabolism; D011869:Radioligand Assay; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*
D011969:Receptors, Histamine H1; D011738:Pyrilamine