COCAINE RECEPTOR--BIOCHEMICAL AND MOLECULAR STUDIES
COCAINE RECEPTOR--BIOCHEMICAL AND MOLECULAR STUDIES
批准号:
3752860
负责人:
M J KUHAR
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
这个项目的目标是阐明多巴胺的性质
英文摘要
The goal of this project is to elucidate the nature of the dopamine
transporter, a key cocaine receptor, in terms of its function and as a
protein. The characterization of this protein as a cocaine binding site
and as an entity of the dopaminergic neuron is essential in
understanding its function.
One of the key findings about the dopamine transporter is that there
appear to be different post-translationally modified forms, at least with
regard to its molecular weight. The differences in molecular weight
appear to be due at least in part to changes in glycosylation, although
it is not possible to rule out other sources of heterogeneity as well.
In a recent study, we have found that over development and aging, the
molecular weight of the dopamine transporter changes. Again, a
significant part of this change is due to differences in glycosylation.
These results indicate that if dopaminergic neurons are used from
immature species, for example for transplant, the transporter is not the
same as that in the fully developed adult.
The mechanisms that regulate the dopamine transporter are not fully
understood. Because of the new knowledge that glutamatergic synapses
result in the elaboration of nitric oxide, and because dopaminergic
synapses have been found adjacent to glutamatergic synapses in striatal
tissue, we tested whether or not nitric oxide would inhibit dopamine
uptake. We found that nitric oxide inhibits dopamine uptake in a time,
dose and temperature dependent fashion. The inhibition of dopamine
uptake occurs at lower concentrations of nitric oxide generator than does
the inhibition of glutamate uptake. These are the first demonstrations
that nitric oxide affects neurotransmitter uptake and could have profound
implications in the way dopamine transport is regulated. The next goal
is to show that this regulation occurs in vivo.
Primary cell cultures of embryonic rat mid-brain cells can be used to
study the transporter with certain advantages. Since it is clear that
these cells are not within the brain, we wanted to test whether or not
the dopamine transporter in these primary cultures was similar to that
in mature rat brain at least, in regard to their pharmacology. We found
that cocaine analogs inhibited dopamine uptake in these cultures in a
fashion that did not differ from that in adult rat brain. We also showed
that the solubilized dopamine transporter can readily be studied by
standard receptor binding techniques. This will facilitate a variety of
experiments.
We continue to make substantial progress in understanding the nature of
the dopamine transporter protein, how it is processed and possible
mechanisms for its regulation.
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会议论文
COCAINE RECEPTOR--BIOCHEMICAL AND MOLECULAR STUDIES
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批准号:5201686
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:M J KUHAR
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依托单位:
DRUG RECEPTORS IN VIVO--ANIMAL MODELS AND IMAGING
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批准号:3775016
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:M J KUHAR
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依托单位:
DRUG RECEPTORS, NEUROTRANSMITTERS AND ADDICTION
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批准号:3775017
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:M J KUHAR
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依托单位:
THE COCAINE RECEPTOR--STRUCTURE/ACTIVITY RELATIONSHIPS AND LIGAND BINDING
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批准号:3752849
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:M J KUHAR
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依托单位:
DRUG RECEPTORS IN VIVO--ANIMAL MODELS AND IMAGING
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批准号:3838611
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:M J KUHAR
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依托单位:
COCAINE RECEPTOR--BIOCHEMICAL AND MOLECULAR STUDIES
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批准号:3775033
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:M J KUHAR
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依托单位:
DRUG RECEPTORS, NEUROTRANSMITTERS AND ADDICTION
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批准号:3853711
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:M J KUHAR
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依托单位:
THE COCAINE RECEPTOR
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批准号:3853708
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:M J KUHAR
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依托单位:
DRUG RECEPTORS, NEUROTRANSMITTERS AND ADDICTION
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批准号:3838614
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:M J KUHAR
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依托单位:
THE COCAINE RECEPTOR--STRUCTURE-ACTIVITY RELATIONSHIPS AND LIGAND BINDING
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批准号:3838612
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:M J KUHAR
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依托单位:
THE COCAINE RECEPTOR--STRUCTURE/ACTIVITY RELATIONSHIPS AND LIGAND BINDING
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批准号:5201651
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:M J KUHAR
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依托单位:
DRUG RECEPTORS IN VIVO
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批准号:3853707
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:M J KUHAR
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依托单位:
DRUG RECEPTORS IN VIVO--ANIMAL MODELS AND IMAGING
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批准号:3752848
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:M J KUHAR
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依托单位:
DRUG RECEPTORS, NEUROTRANSMITTERS AND ADDICTION
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批准号:3752850
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:M J KUHAR
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依托单位:
DRUG RECEPTORS IN VIVO--ANIMAL MODELS AND IMAGING
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批准号:5201650
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:M J KUHAR
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依托单位:
海外基金