Loss of striatal histamine H2 receptors in Huntington's chorea but not in Parkinson's disease: comparison with animal models.
Autoradiographic techniques were used to study the distribution of histamine H2-receptors as labeled with [125I]iodoaminopotentidine in the brains of patients affected by human neurodegenerative pathologies, as compared with control cases. The highest levels of histamine H2 binding sites in control cases were found in the caudate, putamen, and accumbens nuclei. In Huntington's chorea, the levels of histamine H2-receptor binding sites were found to be markedly decreased in virtually all regions examined, particularly in the putamen and globus pallidus lateralis. The loss of binding sites was related to the grade of the disease. Losses were more marked in grade III disease cases. The possible influence of neuroleptic treatment, commonly used in Huntington's patients, was studied by including samples from clinically treated schizophrenic patients. A moderate increase in the densities of [125I]iodoaminopotentidine was found in the globus pallidus of these patients. In Parkinson's disease, the levels of histamine H2-receptor binding sites were found not to be significantly different from those of control cases. These results were comparable with those obtained from unilaterally neurotoxin-lesioned guinea pigs. Similar losses of binding sites were observed in the quinolinic acid lesioned striatal intrinsic neurons in the guinea pig, whereas lesioning dopaminergic cell bodies in the substantia nigra with 6-hydroxydopamine did not produce any significant change. These results strongly suggest that histamine H2-receptors are expressed by striatal neurons, which degenerate in Huntington's chorea, but not by nigral dopaminergic neurons and may play a role in the regulation of the intact striato-nigral pathway.
Martínez-Mir
M I
MI
Departament de Farmacologia, Facultat de Medicina i Odontologia, Universitat de Valencia, Spain.
Pollard
H
H
Moreau
J
J
Traiffort
E
E
Ruat
M
M
Schwartz
J C
JC
Palacios
J M
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006146:Guanidines / Q000378:metabolism*; D006168:Guinea Pigs; D006635:Histamine H2 Antagonists / Q000378:metabolism*; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D010302:Parkinson Disease, Secondary / Q000378:metabolism / Q000473:pathology; D011970:Receptors, Histamine H2 / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values
D006146:Guanidines; D006635:Histamine H2 Antagonists; D007457:Iodine Radioisotopes; D011970:Receptors, Histamine H2; C063279:iodoaminopotentidine