Mutagenesis at the human tachykinin NK2 receptor to define the binding site of a novel class of antagonists

European Journal of Pharmacology

Volumn 488, Issue 1-3, 2004, Pages 61-69

  Meini, Stefania ^a   Bellucci, Francesca ^a   Catalani, Claudio ^a   Cucchi, Paola ^a   Patacchini, Riccardo ^a   Rotondaro, Luigi ^b   Altamura, Maria ^b   Giuliani, Sandro ^a   Giolitti, Alessandro ^b   Maggi, Carlo Alberto ^a  

^a Menarini Ricerche SpA   (Italy)

^b Menarini Biotech ^*  (Italy)

Author keywords

Binding site; G protein coupled receptor; Molecular modelling; Nonpeptide antagonists; Site directed mutagenesis

Indexed keywords

[NALPHA [NALPHA (BENZO[B]THIOPHEN 2 YL)CARBONYL] 1 AMINOCYCLOPENTANE 1 CARBOXYL] DEXTRO PHENYLALANINE N [3 (MORPHOLIN 4 YL)PROPYL]AMIDE; [NGAMMA [NALPHA [NALPHA (BENZO[B]THIOPHEN 2 YL)CARBONYL] 1 AMINOCYCLOHEXAN 1 CARBOXY] DEXTRO PHENYLALANYL] 3 AMINOCYCLOHEXAN 1 CARBOXYLIC ACID N 2 AMINOCYCLOHEXYLAMIDE; MEN 13918; MEN 14268; NEPADUTANT; NEUROKININ 2 RECEPTOR; NEUROKININ 2 RECEPTOR ANTAGONIST; NEUROKININ A; RADIOLIGAND; RHODOPSIN; SAREDUTANT; TACHYKININ RECEPTOR AGONIST; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BINDING KINETICS; BLADDER CONTRACTION; CELL MUTANT; CHO CELL; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG BINDING SITE; DRUG POTENCY; DRUG RECEPTOR BINDING; HUMAN; HUMAN TISSUE; LIGAND BINDING; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; RECEPTOR AFFINITY; SITE DIRECTED MUTAGENESIS; SMOOTH MUSCLE; X RAY CRYSTALLOGRAPHY;

ANIMALS; BENZAMIDES; BINDING SITES; BINDING, COMPETITIVE; CELL MEMBRANE; CHO CELLS; CRICETINAE; DNA, COMPLEMENTARY; GUINEA PIGS; LIGANDS; MALE; MODELS, MOLECULAR; MUSCLE CONTRACTION; MUSCLE, SMOOTH; MUTAGENESIS, SITE-DIRECTED; PEPTIDES, CYCLIC; PIPERIDINES; RADIOLIGAND ASSAY; RATS; RECEPTORS, NEUROKININ-2;

EID: 12144285734     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejphar.2004.02.016     Document Type: Article

References (33)

1. Aharony D., Little J., Thomas C., Powell S., Berry D., Graham A. Isolation and pharmacological characterization of a hamster neurokinin A receptor cDNA. Mol. Pharmacol. 45:1994;9-19.
2. Bellucci F., Meini S., Cucchi P., Catalani C., Reichert W., Zappitelli S., Rotondaro L., Quartara L., Giolitti A., Maggi C.A. A different molecular interaction of bradykinin and the synthetic agonist FR190997 with the human B2 receptor: evidence from mutational analysis. Br. J. Pharmacol. 140:2003;500-506.
3. Bradford M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilising the principle of protein-dye binding. Anal. Biochem. 75:1976;248-254.
4. 2 receptor antagonist. Br. J. Pharmacol. 123:1998;81-91.
5. Ciucci A., Palma C., Riitano D., Manzini S., Werge T.M. Gly166 in the NK1 receptor regulates tachykinin selectivity and receptor conformation. FEBS. Lett. 416:1997;335-338.
6. 3H]SR 48968, a potent nonpeptide radioligand antagonist of the neurokinin-2 receptor. Biochem. Biophys. Res. Commun. 191:1993;1172-1177.
7. Gerard N.P., Eddy R.L. Jr., Shows T.B., Gerard C. The human neurokinin A (substance K) receptor. J. Biol. Chem. 265:1990;20455-20462.
8. Giannotti D., Perrotta E., Di Bugno C., Nannicini R., Harmat N.J.S., Giolitti A., Patacchini R., Renzetti A.R., Rotondaro L., Giuliani S., Altamura M., Maggi C.A. Discovery of potent cyclic pseudopeptide human tachykinin NK-2 receptor antagonists. J. Med. Chem. 43:2000;4041-4044.
9. Giolitti A., Cucchi P., Renzetti A.R., Rotondaro L., Zappitelli S., Maggi C.A. Molecular determinants of peptide and nonpeptide NK-2 receptor antagonists binding sites of the human tachykinin NK-2 receptor by site-directed mutagenesis. Neuropharmacology. 39:2000;1422-1429.
10. Giolitti A., Altamura M., Bellucci F., Giannotti D., Meini S., Patacchini R., Rotondaro L., Zappitelli S., Maggi C.A. Monocyclic human tachykinin NK-2 receptor antagonsits as evolution of a potent bicyclic antagonist: QSAR and site-directed mutagenesis studies. J. Med. Chem. 45:2002;3418-3429.
11. Huang R.-R.C., Yu H., Strader C.D., Fong T.M. Interaction of substance P with the second and seventh transmembrane domains of the neurokinin-1 receptor. Biochemistry. 33:1994;3007-3013.
12. Huang R.R.C., Vicario P.P., Strader C.D., Fong T.M. Identification of residues involved in ligand binding to the neurokinin-2 receptor. Biochemistry. 34:1995;10048-10055.
13. Ireland S.J., Bailey F., Cook A., Hagan R.M., Jordan C.C., Stephens-Smith M.L. Receptors mediating tachykinin-induced contractile responses in guinea-pig trachea. Br. J. Pharmacol. 103:1991;1463-1469.
14. Lecci A., Maggi C.A. Peripheral tachykinin receptors as potential therapeutic targets in visceral diseases. Expert Opin. Ther. Targets. 7:2003;343-362.
15. Lundstrom K., Hawcock A.B., Vargas A., Ward P., Thomas P., Naylor A. Effect of single point mutations of the human tachykinin NK1 receptor on antagonist affinity. Eur. J. Pharmacol. 337:1997;73-81.
16. Kenakin T. Competitive antagonism. Pharmacologic Analysis of Drug-Receptor Interaction. 3rd edn. 1997;331-373 Lippincott-Raven, Philadelphia.
17. Maggi C.A. Evidence for receptor subtypes/species variants of receptors. Buck S.H. The Tachykinin Receptors. 1994;395-470 Humana Press, New Jersey.
18. 2 tachykinin receptor subtypes. Br. J. Pharmacol. 100:1990;588-592.
19. Maggi C.A., Eglezos A., Quartara L., Patacchini R., Giachetti A. Heterogeneity of NK-2 tachykinin receptors in hamster and rabbit smooth muscles. Regul. Peptides. 37:1992;85-93.
20. 2 receptors. J. Pharm. Exp. Ther. 271:1994;1489-1500.
21. Meini S., Cucchi P., Zappitelli S., Rotondaro L., Quartara L., Giolitti A., Maggi C.A. Preliminary mutational analysis of the human kinin B2 receptor for nonpeptide antagonist ligands recognition. Can. J. Physiol. Pharmacol. 80:2002;303-309.
22. Meini S., Cucchi P., Bellucci F., Catalani C., Faiella A., Rotondaro L., Quartara L., Giolitti A., Maggi C.A. Site-directed mutagenesis at the human B2 receptor and molecular modelling to define the pharmacophore of non-peptide bradykinin receptor antagonists. Biochem. Pharmacol. 67:2004;601-609.
23. Palczewski K., Kumasaka T., Hori T., Behnke C.A., Motoshima H., Fox B.A., Le Trong I., Teller C.D., Okada T., Stenkamp R.E., Yamamoto M., Miyano M. Crystal structure of rhodopsin: a G protein-coupled receptor. Science. 289:2000;739-745.
24. 2 receptors in human intestine and urinary bladder. Eur. J. Pharmacol. 398:2000;389-397.
25. 2 receptor. Biochem. Biophys. Res. Comm. 248:1998;78-82.
26. 2 receptor. J. Pharm. Exp. Ther. 290:1999;487-495.
27. Rotondaro L., Mazzanti L., Mele A., Rovera G. High-level expression of a cDNA for human granulocyte colony-stimulating factor in Chinese hamster ovary cells effect of 3′-noncoding sequences. Mol. Biotechnol. 7:1997;231-240.
28. 2 receptor antagonist in the guinea-pig and human colon. Naunyn-Schmiedeberg's Arch. Pharmacol. 356:1997;678-688.
29. Sasai Y., Nakanishi S. Molecular characterization of rat substance K receptor and its mRNAs. Biochem. Biophys. Res. Commun. 165:1989;695-702.
30. Schwartz T.W. Locating ligand-binding sites in 7TM receptors by protein engineering. Curr. Opin. Biotechnol. 5:1994;434-444.
31. Severini C., Improta G., Falconieri-Erspamer G., Salvadori S., Erspamer V. The tachykinin peptide family. Pharmacol. Rev. 54:2002;285-322.
32. Takahashi K., Tanaka A., Hara M., Nakanishi S. The primary structure and gene organization of human substance P and neuromedin K receptors. Eur. J. Biochem. 204:1992;1025-1033.
33. Turcatti G., Zoffmann S., Lowe J.A. III, Drozda S.E., Chassaing G., Schwartz T.W., Chollet A. Characterization of non-peptide antagonist and peptide agonist binding sites of the NK1 receptor with fluorescent ligands. J. Biol. Chem. 34:1997;21167-21175.