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Interaction of the substance P receptor antagonist RP 67580 with the rat brain NK1 receptor expressed in transfected CHO cells. 1993

E Hermans, and A P Jeanjean, and V Fardin, and L Pradier, and C Garret, and P M Laduron, and J N Octave, and J M Maloteaux
Laboratoire de Neurochimie, Université Catholique de Louvain, Brussels, Belgium.

In the present study, we describe the effects of RP 67580, a substance P non-peptide antagonist, in binding and second messenger experiments performed using transfected Chinese hamster ovary cells expressing the rat NK1 receptor. The cDNA sequence encoding the rat brain substance P receptor was transfected in Chinese hamster ovary cells, and cellular clones which stably express the corresponding protein were isolated. [3H]Substance P binding was performed in homogenates of these transfected cells and revealed the presence of NK1 receptors in displacement experiments, using peptide analogs of three mammalian tachykinins (substance P, neurokinin A, neurokinin B). Scatchard analysis indicated a KD value of 0.33 +/- 0.13 nM and a Bmax value of 5.83 +/- 1.16 pmol/mg of protein. RP 67580, a selective NK1-receptor antagonist was found to displace the specific binding of [3H]substance P. When [3H]RP 67580 was used as a ligand, it displayed a high affinity (KD value: 1.22 +/- 0.27 nM) in transfected cell homogenates and only competed with NK1 receptor ligands. Substance P stimulated the hydrolysis of phosphoinositide in a time- and concentration-dependent manner and this effect was mimicked by selective agonists of the NK1 receptor ([Pro9]SP and septide). RP 67580 did not induce any accumulation of inositol phosphates, but was found to inhibit the inositol phosphate increase mediated by substance P, without affecting the maximal response. From these results, one may conclude that the receptor expressed by the transfected Chinese hamster ovary cells revealed similar binding characteristics as the NK1 receptor present in the rat brain and also confirmed the high affinity and the antagonist properties of RP 67580.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D007295 Inositol Phosphates Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID. Inositol Phosphate,Phosphate, Inositol,Phosphates, Inositol
D003001 Cloning, Molecular The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells. Molecular Cloning
D003412 Cricetulus A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research. Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D006868 Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013373 Substance P An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. Euler-Gaddum Substance P,Hypothalamic Substance P,SP(1-11),Euler Gaddum Substance P,Substance P, Euler-Gaddum,Substance P, Hypothalamic
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections
D016466 CHO Cells CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells. CHO Cell,Cell, CHO,Cells, CHO

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