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Intracellular [3H]dopamine binding sites in normal and malignant cells: relationships to cell proliferation
B M Markaverich1, R R Gregory, M A Alejandro
1Center for Biotechnology, Baylor College of Medicine, Woodlands, Texas 77381.
Abstract:
Dopamine interaction with target cells undoubtably involves binding to plasma membrane receptors. However, the well documented cell growth inhibitory activity of this catecholamine suggests nuclear regulation. To evaluate this possibility, we determined the intracellular localization and binding of [3H]dopamine in human retinoblastoma (Y-79 cells), normal mouse fibroblasts (LM-cells), and in the rat uterus. Cytosol and purified nuclear preparations devoid of plasma membrane components contained specific, saturable, high affinity (Kd approximately 20 nM) binding sites for [3H]dopamine. The nuclear binding affinity for dopamine, L-dopa, and L-dopa methyl ester correlated with the inhibitory effects of these compounds on cell proliferation, suggesting that intracellular dopamine binding sites may also be involved in cellular response to catecholamines.
Insights
Dopamine, a catecholamine, binds to specific nuclear sites in cells, influencing cell growth. This suggests dopamine
Area of Science:
- Cell Biology
- Neurochemistry
- Molecular Pharmacology
Background:
- Dopamine's interaction with target cells typically involves plasma membrane receptors.
- However, dopamine's known cell growth inhibitory effects suggest potential intracellular or nuclear roles.
Purpose of the Study:
- To investigate the intracellular localization and binding of dopamine within cells.
- To determine if nuclear dopamine binding sites exist and correlate with cellular responses.
Main Methods:
- Utilized radiolabeled [3H]dopamine to assess binding.
- Examined dopamine binding in human retinoblastoma (Y-79) cells, mouse fibroblasts (LM-cells), and rat uterus.
- Analyzed binding in cytosol and purified nuclear preparations, excluding plasma membrane components.
Main Results:
- Identified specific, saturable, high-affinity (Kd ≈ 20 nM) [3H]dopamine binding sites in both cytosol and purified nuclei.
- Observed that nuclear binding affinity for dopamine and related compounds correlated with their cell proliferation inhibitory effects.
Conclusions:
- Dopamine binds to specific intracellular sites, including the nucleus.
- Nuclear dopamine binding may play a significant role in mediating the catecholamine's effects on cell proliferation.