PROPENTOFYLLINE INHIBITS POLYMORPHONUCLEAR LEUKOCYTE RECRUITMENT IN-VIVO BY A MECHANISM INVOLVING ADENOSINE A(2A) RECEPTORS

Propentofylline is an atypical xanthine derivative that blocks adenosi ne uptake and has been shown to protect against ischemia-induced cereb ral damage. We have studied the effect of propentofylline on recruitme nt of polymorphonuclear leukocytes during acute peritonitis induced by zymosan in mice. Following i.p. injection of zymosan, recruitment of polymorphonuclear leukocytes, reflected by myeloperoxidase activity in the peritoneal cavity, increased from 2 h onwards, peaked at 4 h and then decreased gradually. Propentofylline antagonized the zymosan-indu ced peritoneal myeloperoxidase accumulation in a concentration-depende nt manner. This effect of propentofylline was counteracted by the non- selective adenosine receptor antagonist theophylline (50 mg/kg), and b y the selective adenosine A(2A) receptor antagonists, chloro-1-phenyl- [1,2,4]-triazolo[4,3-a]quinoxaline (CP 66713) and -dipropyl-8-[3,4-dim ethoxystyryl]-7-methylxanthine (KF 17387) (both at 2 mg/kg). The resul ts indicate that propentofylline can reduce polymorphonuclear leukocyt e recruitment in vivo and that this effect is related to an action on adenosine A(2A) receptors.