WS9326A, A NOVEL TACHYKININ ANTAGONIST ISOLATED FROM STREPTOMYCES-VIOLACEUSNIGER NO-9326 .2. BIOLOGICAL AND PHARMACOLOGICAL PROPERTIES OF WS9326A AND TETRAHYDRO-WS9326A (FK224)

被引：29

作者：

HASHIMOTO, M

HAYASHI, K

MURAI, M

FUJII, T

NISHIKAWA, M

KIYOTO, S

OKUHARA, M

KOHSAKA, M

IMANAKA, H

机构：

[1] FUJISAWA PHARMACEUT CO LTD,EXPLORATORY RES LABS,5-2-3 TOKODAI,TSUKUBA,IBARAKI 30026,JAPAN

[2] FUJISAWA PHARMACEUT CO LTD,NEW DRUG RES LABS,OSAKA 532,JAPAN

来源：

JOURNAL OF ANTIBIOTICS | 1992年 / 45卷 / 07期

关键词：

D O I：

10.7164/antibiotics.45.1064

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

WS9326A binds competitively to [H-3]substance P (NK-1 receptor) binding sites on guinea-pig lung membranes (IC50 = 3.6 x 10(-6) M), and acts as a tachykinin antagonist in various functional assays. WS9326A inhibited tracheal constrictions produced by exogenously added substance P and neurokinin A, with IC50 values of 9.7 x 10(-6) M and 3.5 x 10(-6) M, respectively. WS9326A inhibited neurokinin A-induced bronchoconstriction in a dose dependent manner when administered to guinea-pigs intravenously together with neurokinin A, and was also effective in preventing capsaicin-induced bronchoconstriction, which is known to be caused by release of endogenous tachykinins (substance P and neurokinin A). FK224 (tetrahydro-WS9326A; catalytic hydrogenation of WS9326A gave FK224) was more potent than WS9326A in the [H-3]substance P receptor binding assay using guinea-pig lung membrane (IC50 = 1.0 x 10(-7) M).

引用

页码：1064 / 1070

页数：7

共 23 条

[1] NEUROPEPTIDES IN HUMAN AIRWAYS - FUNCTION AND CLINICAL IMPLICATIONS
BARNES, PJ
[J]. AMERICAN REVIEW OF RESPIRATORY DISEASE, 1987, 136 (06): : S77 - S83
[2] BARNES PJ, 1988, PHARMACOL REV, V40, P49
[3] BUCK SH, 1986, PHARMACOL REV, V38, P179
[4] EFFECT OF SUBSTANCE-P ON CARDIOVASCULAR AND RESPIRATORY-FUNCTION IN SUBJECTS
FULLER, RW
MAXWELL, DL
DIXON, CMS
MCGREGOR, GP
BARNES, VF
BLOOM, SR
BARNES, PJ
[J]. JOURNAL OF APPLIED PHYSIOLOGY, 1987, 62 (04) : 1473 - 1479
[5] WS9326A, A NOVEL TACHYKININ ANTAGONIST ISOLATED FROM STREPTOMYCES-VIOLACEUSNIGER NO-9326
HAYASHI, K
HASHIMOTO, M
SHIGEMATSU, N
NISHIKAWA, M
EZAKI, M
YAMASHITA, M
KIYOTO, S
OKUHARA, M
KOHSAKA, M
IMANAKA, H
[J]. JOURNAL OF ANTIBIOTICS, 1992, 45 (07) : 1055 - 1063
[6] HUA XY, 1985, REGUL PEPTIDES, V13, P1, DOI 10.1016/0167-0115(85)90082-5
[7] EFFECT OF INHALED SUBSTANCE-P AND NEUROKININ-A ON THE AIRWAYS OF NORMAL AND ASTHMATIC SUBJECTS
JOOS, G
PAUWELS, R
VANDERSTRAETEN, M
[J]. THORAX, 1987, 42 (10) : 779 - 783
[8] SUBSTANCE-P ANTAGONISTS AND THE ROLE OF TACHYKININS IN NON-CHOLINERGIC BRONCHOCONSTRICTION
KARLSSON, JA
FINNEY, MJB
PERSSON, CGA
POST, C
[J]. LIFE SCIENCES, 1984, 35 (26) : 2681 - 2691
[9] KARLSSON JA, 1985, TACHYKININ ANTAGONIS, P181
[10] LUNDBERG JM, 1984, CELL TISSUE RES, V235, P251

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