cDNA sequence and heterologous expression of the human neurokinin-3 receptor.
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.
Huang
R R
RR
Department of Molecular Pharmacology and Biochemistry, Merck Research Laboratories, Rahway, NJ 07065.
Cheung
A H
AH
Mazina
K E
KE
Strader
C D
CD
Fong
T M
TM
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000502:physiology*; D002460:Cell Line; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000378:metabolism / Q000494:pharmacology*; D009865:Oocytes / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013373:Substance P / Q000494:pharmacology; D014162:Transfection; D014981:Xenopus
D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D012333:RNA, Messenger; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D011994:Recombinant Proteins; D013373:Substance P; D015288:Neurokinin A; D004247:DNA