THE NONPEPTIDE TACHYKININ NK2 RECEPTOR ANTAGONIST SR-48968 INTERACTS WITH HUMAN, BUT NOT RAT, CLONED TACHYKININ NK3 RECEPTORS

被引：26

作者：

CHUNG, FZ ^{[1
]}

WU, LH ^{[1
]}

VARTANIAN, MA ^{[1
]}

WATLING, KJ ^{[1
]}

GUARD, S ^{[1
]}

WOODRUFF, GN ^{[1
]}

OXENDER, DL ^{[1
]}

机构：

[1] PARKE DAVIS NEUROSCI RES CTR,CAMBRIDGE CB2 2QB,CAMBS,ENGLAND

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1994年 / 198卷 / 03期

关键词：

D O I：

10.1006/bbrc.1994.1138

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

SR 48968, a non-peptide tachykinin NK2 receptor antagonist, has been shown to possess sub-micromolar affinity for NK3 receptors present in the guinea pig. In the present study, we have compared the binding affinities of SR 48968 to the cloned human and rat NK3 receptors expressed in CHO cells. Using [125I]-[MePhe7]-neurokinin B as the radioligand, SR48968 displayed an IC50 value of 350 nM for the human NK3 receptor as compared with a value of greater than 10 μM for the rat NK3 receptor. Exposure of cells transfected with human NK3 receptor cDNA to [Pro7]-neurokinin B increased inositol phospholipid turnover in a concentration-dependent manner and this response was blocked competitively by SR 48968. Our results demonstrate that SR 48968 is an antagonist at the human NK3 receptor and may be a useful tool for elucidating the species-dependent variations in the non-peptide antagonist binding site(s) on the NK3 receptor. © 1994 Academic Press. All rights reserved.

引用

页码：967 / 972

页数：6

共 23 条

[1] NEUROKININ A (NK2) RECEPTOR REVISITED WITH SR-48968, A POTENT NONPEPTIDE ANTAGONIST
ADVENIER, C
ROUISSI, N
NGUYEN, QT
EMONDSALT, X
BRELIERE, JC
NELIAT, G
NALINE, E
REGOLI, D
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 184 (03) : 1418 - 1424
[2] INVESTIGATION INTO SPECIES VARIANTS IN TACHYKININ NK1 RECEPTORS BY USE OF THE NONPEPTIDE ANTAGONIST, CP-96,345
BERESFORD, IJM
BIRCH, PJ
HAGAN, RM
IRELAND, SJ
[J]. BRITISH JOURNAL OF PHARMACOLOGY, 1991, 104 (02) : 292 - 293
[3] BOYLE SJ, 1993, BRIT J PHARMACOL, V108, pP24
[4] CHUNG FZ, 1988, J BIOL CHEM, V263, P4052
[5] SR-48968, A NEUROKININ-A (NK2) RECEPTOR ANTAGONIST
EMONDSALT, X
ADVENIER, C
CROCI, T
MANARA, L
NELIAT, G
PONCELET, M
PROIETTO, V
SANTUCCI, V
SOUBRIE, P
VANBROECK, D
VILAIN, P
LEFUR, G
BRELIERE, JC
[J]. REGULATORY PEPTIDES, 1993, 46 (1-2) : 31 - 36
[6] FONG TM, 1992, J BIOL CHEM, V267, P25668
[7] ANTINOCICEPTIVE PROPERTIES AND INHIBITION OF NEUROGENIC INFLAMMATION WITH POTENT SP ANTAGONISTS BELONGING TO PERHYDROISOINDOLONES
GARRET, C
CARRUETTE, A
FARDIN, V
MOUSSAOUI, S
MONTIER, F
PEYRONEL, JF
LADURON, PM
[J]. REGULATORY PEPTIDES, 1993, 46 (1-2) : 24 - 30
[8] PHARMACOLOGICAL PROPERTIES OF A POTENT AND SELECTIVE NONPEPTIDE SUBSTANCE-P ANTAGONIST
GARRET, C
CARRUETTE, A
FARDIN, V
MOUSSAOUI, S
PEYRONEL, JF
BLANCHARD, JC
LADURON, PM
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (22) : 10208 - 10212
[9] SPECIES-DIFFERENCES IN AFFINITIES OF NONPEPTIDE ANTAGONISTS FOR SUBSTANCE-P RECEPTORS
GITTER, BD
WATERS, DC
BRUNS, RF
MASON, NR
NIXON, JA
HOWBERT, JJ
[J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1991, 197 (2-3) : 237 - 238
[10] GRIMSON P, 1993, BRIT J PHARMACOL, V110, pP59

← 1 2 3 →