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Titolo:
Synergistic antiallergic activity of combined histamine H-1- and cysteinylleukotriene(1)-receptor blockade in human bronchus
Autore:
Ruck, LM; Rizzo, CA; Anthes, JC; Eckel, S; Egan, RW; Cuss, FM; Hey, JA;
Indirizzi:
Schering Plough Res Inst, Kenilworth, NJ 07033 USA Schering Plough Res Inst Kenilworth NJ USA 07033 Kenilworth, NJ 07033 USA
Titolo Testata:
LIFE SCIENCES
fascicolo: 25, volume: 68, anno: 2001,
pagine: 2825 - 2834
SICI:
0024-3205(20010511)68:25<2825:SAAOCH>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
INOSITOL PHOSPHOLIPID HYDROLYSIS; HUMAN MAST-CELLS; LEUKOTRIENE ANTAGONISTS; RECEPTOR ANTAGONIST; AIRWAY-OBSTRUCTION; CRYOPRESERVATION; CONTRACTIONS; INHIBITION; RELEASE; POTENT;
Keywords:
histamine H-1-receptor; cysteinyl leukotriene(1)-receptor; chlorpheniramine; MK-571; L-660,711; allergic bronchospasm; isolated human bronchus; passive sensitization; human cord blood mast cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Ruck, LM Schering Plough Res Inst, 2015 Galloping Hill Rd,K-15-1,1600, Kenilworth, NJ 07033 USA Schering Plough Res Inst 2015 Galloping Hill Rd,K-15-1,1600 Kenilworth NJ USA 07033
Citazione:
L.M. Ruck et al., "Synergistic antiallergic activity of combined histamine H-1- and cysteinylleukotriene(1)-receptor blockade in human bronchus", LIFE SCI, 68(25), 2001, pp. 2825-2834

Abstract

Mast cell histamine (HA) and cysteinyl leukotrienes (CysLT) account for most of the early phase bronchospasm in asthma. However, activation of the smooth muscle CysLT(1)-receptor plays a major role in asthmatic bronchospasms. CysLT-receptor antagonists or CysLT-synthesis inhibitors are efficacious in asthma but do not completely abolish asthmatic bronchospasms. A recent clinical study showed that combined antagonists loratadine (H-1) and zafirlukast (CysLT(1)) were more effective against allergic bronchospasms than either drug alone. We examined the combined efficacy of H-1- and CysLT(1)-receptor antagonists in allergic human bronchus. The H-1- and CysLT(1)-receptorantagonists chlorpheniramine (CTM; 1 muM) and MK-571 (0.03 muM), were tested alone and in combination, against anti-human IgE antibody (Ab)-induced contractions of passively sensitized isolated human bronchus. Ab-induced allergic contractions were reduced 15% and 36% by CTM (1 muM) and MK-571 (0.03muM), respectively. Combined CTM (1 muM) and MK-571 (0.03 muM) significantly inhibited the Ab response by 87%. Mechanistic investigations in isolatedhuman bronchus and cultured human cord blood mast cells suggest that H-1- and CysLT-receptor interactions likely occur at the airway smooth muscle level. CTM and MK-571 synergistically inhibited human allergic bronchospasm in the present in vitro model. The mechanism underlying this synergistic activity requires further investigation. (C) 2001 Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 00:17:49