In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 82, No. 3 ( 1985-02), p. 672-676
Abstract:
Platelet-activating factor (PAF) is a potent lipid mediator of inflammation and asthma. Using a receptor preparation of rabbit platelet membranes, we identified a novel antagonist of PAF in the methylene chloride extract of a Chinese herbal plant, haifenteng (Piper futokadsura). The active antagonist, kadsurenone, was isolated and characterized in several in vitro and in vivo assays. It is a specific and competitive inhibitor of PAF binding to its receptor with a Ki of 5.8 X 10(-8) M vs. a Ki of 6.3 X 10(-9) M for PAF itself. It inhibits PAF-induced aggregation of rabbit platelets and human neutrophils at 2.4-24 microM, without showing any PAF agonistic activity. It potently inhibits PAF-induced degranulation of human neutrophils at 2.5-50 microM, also without any agonist activity. Kadsurenone is active orally at 25-50 mg/kg of body weight in blocking PAF-induced cutaneous permeability in the guinea pig. It also inhibits PAF-induced increases of hematocrit and circulating N-acetylglucosaminidase in the rat at greater than 10 mg/kg i.p. in a dose-dependent manner. Kadsurenone does not interfere with the function of several pharmacological mediators and receptors tested. Its structural specificity is evidenced by the poor PAF-antagonistic activities of three related structures isolated from the same haifenteng extract.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.82.3.672
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1985
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
Permalink