Abstract
Functional cDNA clones encoding the human neurokinin-3 receptor were isolated from human brain mRNA. The cloned human neurokinin-3 receptor was expressed in COS cells and Xenopus oocytes, where peptide binding affinity and intracellular effector activation were determined. Neurokinin B is the most potent agonist, followed by eledoisin, substance K and substance P. The binding affinities of these peptides at the human neurokinin-3 receptor differ quantitatively from the rat receptor, implying a functional consequence of the sequence divergence between the two species. Heterologous expression in oocytes revealed that, unlike the neurokinin-1 receptor, the efficacy of ion channel activation mediated by the neurokinin-3 receptor does not approximate the binding affinity. The heterologous expression of the human neurokinin-3 receptor will facilitate further investigation into its biochemical functions.
MeSH terms
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Amino Acid Sequence
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Animals
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Binding, Competitive
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Brain / physiology*
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Cell Line
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Chloride Channels
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Chlorides / metabolism
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Cloning, Molecular
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DNA / genetics*
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Gene Expression
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Humans
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Kinetics
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Membrane Proteins / drug effects
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Membrane Proteins / physiology
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Molecular Sequence Data
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Neurokinin A / metabolism
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Neurokinin A / pharmacology*
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Oocytes / physiology
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RNA, Messenger / genetics*
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Rats
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Receptors, Neurokinin-2
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Receptors, Neurotransmitter / genetics*
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Receptors, Neurotransmitter / metabolism
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Receptors, Neurotransmitter / physiology
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Recombinant Proteins / metabolism
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Sequence Homology, Nucleic Acid
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Substance P / pharmacology
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Transfection
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Xenopus
Substances
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Chloride Channels
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Chlorides
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Membrane Proteins
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RNA, Messenger
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Receptors, Neurokinin-2
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Receptors, Neurotransmitter
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Recombinant Proteins
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Substance P
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Neurokinin A
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DNA
Associated data
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GENBANK/D10556
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GENBANK/M89473
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GENBANK/M97582
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GENBANK/M97583
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GENBANK/M97584
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GENBANK/M97585
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GENBANK/M97586
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GENBANK/M97587
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GENBANK/M97588
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GENBANK/M97589