Selective inhibition of phospholipases by atiprimod, a macrophage targeting antiarthritic compound.
Toxicol Appl Pharmacol
; 159(1): 9-17, 1999 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-10448120
ABSTRACT
Azaspiranes are cationic amphiphilic compounds that are active in a number of models of autoimmune disease and transplantation. Repeated administration of cationic amphiphiles induces phospholipid accumulation in a variety of species. The present study was conducted to explore the mechanism of phospholipid accumulation in rats caused by treatment with the novel azaspirane, SK&F 106615 (atiprimod). Atiprimod inhibited the activities of partially purified phospholipases A(2) and C, but not D, in a noncompetitive manner in vitro. Treatment of rats for 28 days with 10 mg/kg/day of atiprimod increased the contents of arachidonate-containing molecular species within plasmalogen subclasses of hepatic phosphatidylcholine and phosphatidylethanolamine. In contrast, diacyl-linked species were not affected, indicating a selective effect upon an hepatic plasmalogen-selective phospholipase A(2). Taken together, the data suggest that the beneficial effects of atiprimod in autoimmune diseases may involve inhibition of phospholipase A(2) and C activities. Further, the data suggest that atiprimod is a selective inhibitor of plasmalogen-selective phospholipase A(2) in vivo.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfolipases
/
Fosfolipídeos
/
Compostos de Espiro
/
Anti-Inflamatórios não Esteroides
/
Macrófagos Alveolares
Limite:
Animals
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos