Abstract
Substance P (SP) triggers responses in astrocytoma cells, which are considered important for proliferation and neuroimmunomodulatory activity. In this study, we compared the effects of SP with those of the novel tachykinin Hemokinin-1 (HK-1) in the human astrocytoma cell line U-251 MG. We show that U-251 MG cells express high levels of Neurokinin-1 (NK-1) receptors. The binding affinities of 125I-SP and 125I-mHK-1 to these receptors were in a similar, subnanomolar range. HK-1 and SP stimulated Ca2+ mobilization and induced increased cytokine mRNA expression. A specific NK-1 receptor antagonist blocked the observed effects. We conclude that there are no qualitative differences in SP and HK-1-evoked responses, suggesting that both peptides act through NK-1 receptors in U-251 MG cells. Moreover, we show TAC4 mRNA expression in gliomas, indicating a possible involvement of HK-1 in glioma biology.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Astrocytoma
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Blotting, Northern / methods
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Calcium / metabolism
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Cell Count / methods
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Cell Line, Tumor
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Cytokines / genetics
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Cytokines / metabolism
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Dose-Response Relationship, Drug
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Gene Expression Regulation, Neoplastic / drug effects*
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Hexokinase / pharmacokinetics
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Hexokinase / pharmacology*
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Humans
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Immunohistochemistry / methods
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Iodine Isotopes / pharmacokinetics
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Mice
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Protein Binding / drug effects
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Protein Precursors / pharmacokinetics
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Protein Precursors / pharmacology*
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RNA, Messenger / biosynthesis
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Radioligand Assay / methods
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Receptors, Neurokinin-1 / genetics
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Receptors, Neurokinin-1 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Substance P / pharmacokinetics
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Substance P / pharmacology*
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Tachykinins / pharmacokinetics
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Tachykinins / pharmacology*
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Time Factors
Substances
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Cytokines
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Iodine Isotopes
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Protein Precursors
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RNA, Messenger
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Receptors, Neurokinin-1
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Tac4 protein, mouse
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Tachykinins
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Substance P
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HK1 protein, human
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Hexokinase
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Calcium