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Titolo:
EFFECT OF PF-10040 ON PAF-INDUCED AIRWAY RESPONSES IN NEONATALLY IMMUNIZED RABBITS
Autore:
HERD CM; DONIGIGALE D; SHOUPE TS; KILFEATHER SA; OKIJI SA; PAGE CP;
Indirizzi:
KINGS COLL LONDON,DEPT PHARMACOL,MANRESA RD LONDON SW3 6LX ENGLAND PURDUE FREDERICK CO,INT MOLEC DISCOVERY NORWALK CT 00000
Titolo Testata:
British Journal of Pharmacology
fascicolo: 1, volume: 111, anno: 1994,
pagine: 7 - 12
SICI:
0007-1188(1994)111:1<7:EOPOPA>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLATELET-ACTIVATING-FACTOR; INDUCED BRONCHIAL HYPERRESPONSIVENESS; GUINEA-PIGS; ASTHMA; EOSINOPHILIA; ACCUMULATION; ANTAGONIST; CAPSAICIN; ANTIGEN;
Keywords:
PAF; AIRWAYS; INFLAMMATION; AIRWAY HYPERRESPONSIVENESS; NEONATALLY IMMUNIZED RABBIT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
19
Recensione:
Indirizzi per estratti:
Citazione:
C.M. Herd et al., "EFFECT OF PF-10040 ON PAF-INDUCED AIRWAY RESPONSES IN NEONATALLY IMMUNIZED RABBITS", British Journal of Pharmacology, 111(1), 1994, pp. 7-12

Abstract

1 PF 10040 displaced [H-3]-PAF from binding sites on rabbit plateletswith an IC50 = 1.07 x 10(-5) M, which was approximately three orders of magnitude below that of a standard PAF antagonist WEB 2086 (IC50 = 4.23 x 10(-9) M). 2 PF 10040 at doses of 5 and 10 mg (direct intratracheal administration) had no effect on the acute bronchoconstriction induced by PAF in neonatally immunized rabbits (airway resistance R(L) or dynamic compliance C-dyn) However, the PAF-induced increase in airway responsiveness to inhaled histamine was significantly inhibited (R(L) and C-dyn) by both doses of PF 10040. 3 PF 10040 (5 and 10 mg) significantly inhibited the total pulmonary cell infiltration and neutrophil influx induced by PAF as assessed by bronchoalveolar lavage. PAF-induced eosinophil infiltration into the airways was significantly inhibited in rabbits that received only 10 mg PF 10040. 4 We suggest from the results of the present study that PF 10040 does not exert an inhibitory effect on PAF-induced airway responses solely via antagonism of the PAF receptor located on platelets, as PF 10040 significantly inhibited PAF-induced airway hyperresponsiveness in the absence of an effect on the acute bronchospasm induced by PAF. 5 We provide further evidence that pulmonary eosinophil infiltration and the development of airwayhyperresponsiveness are not causally related events as the lower doseof PF 10040 (5 mg) significantly inhibited PAF-induced airway hyperresponsiveness yet was without effect on the eosinophil influx.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/09/20 alle ore 18:06:55