Microtopography of D1 dopaminergic binding sites in the human substantia nigra: an autoradiographic study.
Identifieur interne : 000A69 ( Ncbi/Curation ); précédent : 000A68; suivant : 000A70Microtopography of D1 dopaminergic binding sites in the human substantia nigra: an autoradiographic study.
Auteurs : F. Thibaut [France] ; E C Hirsch ; R. Raisman ; F. Javoy-Agid ; Yves Agid [France]Source :
- Neuroscience [ 0306-4522 ] ; 1990.
English descriptors
- KwdEn :
- Acetylcholinesterase (metabolism), Aged, Aged, 80 and over, Autoradiography, Benzazepines (metabolism), Benzazepines (pharmacology), Corpus Striatum (pathology), Female, Humans, Huntington Disease (metabolism), Huntington Disease (pathology), Immunohistochemistry, Kinetics, Male, Mesencephalon (enzymology), Parkinson Disease (metabolism), Parkinson Disease (pathology), Receptors, Dopamine (metabolism), Receptors, Dopamine D1, Substantia Nigra (anatomy & histology), Substantia Nigra (metabolism), Tyrosine 3-Monooxygenase (metabolism).
- MESH :
- chemical , metabolism : Acetylcholinesterase, Benzazepines, Receptors, Dopamine, Tyrosine 3-Monooxygenase.
- chemical , pharmacology : Benzazepines.
- anatomy & histology : Substantia Nigra.
- enzymology : Mesencephalon.
- metabolism : Huntington Disease, Parkinson Disease, Substantia Nigra.
- pathology : Corpus Striatum, Huntington Disease, Parkinson Disease.
- Aged, Aged, 80 and over, Autoradiography, Female, Humans, Immunohistochemistry, Kinetics, Male, Receptors, Dopamine D1.
Abstract
The autoradiographic distribution of D1 dopaminergic binding sites was studied in the human ventral mesencephalon using the D1 antagonist [3H]SCH 23390. [3H]SCH 23390 binding was characterized by a single class of sites with a Kd of 2.5 nM and a Bmax of 31 fmol/mg of tissue. The density of [3H]SCH 23390 binding sites was high in the substantia nigra, moderate in the ventral tegmental area and low in the peri- and retrorubral field (catecholaminergic region A8). Binding densities were similar in pars compacta and pars reticulata of the substantia nigra, except for a peak value of high [3H]SCH 23390 in the pars reticulata, at a level just ventral to a zone of hyperdensity of melanized dopaminergic neurons in the pars compacta. The anatomical organization of the human ventral mesencephalon was analysed on adjacent sections stained for acetylcholinesterase histochemistry and tyrosine hydroxylase, substance P, dynorphin B, somatostatin and methionine-enkephalin immunohistochemistry, respectively. The similarity in distribution of [3H]SCH 23390 binding sites and substance P or dynorphin B immunoreactivity suggests that D1 binding sites are mainly located on the striatonigral projections. In accordance with these results: (1) the density of [3H]SCH 23390 binding sites was reduced in the substantia nigra of a patient with Huntington's chorea, a disease associated with a degeneration of striatonigral neurons; (2) the density of [3H]SCH 23390 binding sites was unaffected in the substantia nigra of a patient with Parkinson's disease, a disorder characterized by a marked loss in nigral tyrosine hydroxylase-positive neurons. [3H]SCH 23390 binding sites showed a characteristic, heterogeneous distribution within the human ventral mesencephalon, confirming data obtained in other species. The preferential localization of D1 dopamine receptors on striatonigral projections in human brain suggests that pharmacological manipulation of these receptors modulates the activity of striatonigral pathways, thereby affecting the various outputs of the nigral complex.
PubMed: 1983469
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pubmed:1983469Le document en format XML
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<series><title level="j">Neuroscience</title>
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<term>Benzazepines (metabolism)</term>
<term>Benzazepines (pharmacology)</term>
<term>Corpus Striatum (pathology)</term>
<term>Female</term>
<term>Humans</term>
<term>Huntington Disease (metabolism)</term>
<term>Huntington Disease (pathology)</term>
<term>Immunohistochemistry</term>
<term>Kinetics</term>
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<term>Mesencephalon (enzymology)</term>
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<term>Parkinson Disease (pathology)</term>
<term>Receptors, Dopamine (metabolism)</term>
<term>Receptors, Dopamine D1</term>
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<term>Substantia Nigra (metabolism)</term>
<term>Tyrosine 3-Monooxygenase (metabolism)</term>
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<term>Tyrosine 3-Monooxygenase</term>
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<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Huntington Disease</term>
<term>Parkinson Disease</term>
<term>Substantia Nigra</term>
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<term>Huntington Disease</term>
<term>Parkinson Disease</term>
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<front><div type="abstract" xml:lang="en">The autoradiographic distribution of D1 dopaminergic binding sites was studied in the human ventral mesencephalon using the D1 antagonist [3H]SCH 23390. [3H]SCH 23390 binding was characterized by a single class of sites with a Kd of 2.5 nM and a Bmax of 31 fmol/mg of tissue. The density of [3H]SCH 23390 binding sites was high in the substantia nigra, moderate in the ventral tegmental area and low in the peri- and retrorubral field (catecholaminergic region A8). Binding densities were similar in pars compacta and pars reticulata of the substantia nigra, except for a peak value of high [3H]SCH 23390 in the pars reticulata, at a level just ventral to a zone of hyperdensity of melanized dopaminergic neurons in the pars compacta. The anatomical organization of the human ventral mesencephalon was analysed on adjacent sections stained for acetylcholinesterase histochemistry and tyrosine hydroxylase, substance P, dynorphin B, somatostatin and methionine-enkephalin immunohistochemistry, respectively. The similarity in distribution of [3H]SCH 23390 binding sites and substance P or dynorphin B immunoreactivity suggests that D1 binding sites are mainly located on the striatonigral projections. In accordance with these results: (1) the density of [3H]SCH 23390 binding sites was reduced in the substantia nigra of a patient with Huntington's chorea, a disease associated with a degeneration of striatonigral neurons; (2) the density of [3H]SCH 23390 binding sites was unaffected in the substantia nigra of a patient with Parkinson's disease, a disorder characterized by a marked loss in nigral tyrosine hydroxylase-positive neurons. [3H]SCH 23390 binding sites showed a characteristic, heterogeneous distribution within the human ventral mesencephalon, confirming data obtained in other species. The preferential localization of D1 dopamine receptors on striatonigral projections in human brain suggests that pharmacological manipulation of these receptors modulates the activity of striatonigral pathways, thereby affecting the various outputs of the nigral complex.</div>
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