Abstract
Neurokinin (NK)-1 and NK-2 receptors regulate hematopoiesis by interacting with neurotransmitters that belong to the tachykinin. This report studies the relationship between NK-1 and NK-2 in primary human bone marrow (BM) stroma, which supports hematopoiesis. Use of NK receptor antagonists and deficient stromal cells indicate that the neurotransmitter, substance P (SP), could exert dual hematopoietic effects (inhibitory or stimulatory), depending on the interacting receptor and crosstalk between NK-1 and NK-2. Cloning and identification of the minimal promoter for NK-2 and comparison with NK-1 promoter showed that the hematopoietic functions of NK receptors involve receptor crosstalk and the particular cytokine (IL-3, GM-CSF, TGF-beta or IL-1alpha). Crosstalk between NK-1 and NK-2 adds to communication within neural-hematopoietic axis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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5' Untranslated Regions / drug effects
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Base Sequence
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Bone Marrow Cells / cytology
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / metabolism
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Cell Division / physiology
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Cells, Cultured
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Cloning, Molecular / methods
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Cytokines / pharmacology
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Down-Regulation / drug effects
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Gene Deletion
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Hematopoiesis / genetics
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Hematopoiesis / physiology*
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / drug effects
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Hematopoietic Stem Cells / metabolism
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Humans
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Molecular Sequence Data
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Neurokinin-1 Receptor Antagonists
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Promoter Regions, Genetic* / drug effects
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Promoter Regions, Genetic* / genetics
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RNA, Messenger / metabolism
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Receptor Cross-Talk / physiology*
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Receptors, Neurokinin-1 / genetics
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Receptors, Neurokinin-1 / physiology*
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Receptors, Neurokinin-2 / antagonists & inhibitors
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Receptors, Neurokinin-2 / chemistry*
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Receptors, Neurokinin-2 / genetics
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Receptors, Neurokinin-2 / physiology*
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Stromal Cells / drug effects
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Stromal Cells / metabolism
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Substance P / pharmacology
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Transfection
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Up-Regulation / drug effects
Substances
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5' Untranslated Regions
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Cytokines
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Neurokinin-1 Receptor Antagonists
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RNA, Messenger
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Receptors, Neurokinin-1
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Receptors, Neurokinin-2
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Substance P