Adenosine analogs: potentiation of bradykinin-induced plasma exudation in rat skin and prevention by caffeine and theophylline.

Adenosine and various analogs potentiated plasma exudation elicited by bradykinin in rat skin using 125I-labelled bovine serum albumin (125I-BSA) as a tracer. L-N6-Phenylisopropyladenosine (L-PIA) was much more effective than D-PIA, adenosine, N6-cyclohexyladenosine (CHA) and 2-chloroadenosine, all of which were comparable in activity. Adenosine 5'-cyclopropylcarboxamide was the least effective analog. Caffeine and theophylline had no effect on basal or bradykinin-elicited plasma exudation, while inhibiting plasma exudation elicited by L-PIA, CHA or a combination of bradykinin and L-PIA. 8-Phenyltheophylline was more potent than caffeine or theophylline versus the bradykinin and L-PIA combination. 2',5'-Dideoxyadenosine, a P-site inhibitor of adenylate cyclase, had no effect on plasma exudation elicited by bradykinin, L-PIA or a combination of bradykinin and L-PIA, but did inhibit plasma exudation elicited by prostaglandin E1 (PGE1) or a bradykinin-PGE1-combination. The antihistamine cyproheptadine slightly reduced plasma exudation elicited by a bradykinin-PGE1 combination. The results suggest that adenosine potentiates bradykinin-induced plasma exudation via an adenosine receptor and that histamine may be involved to some extent in the phenomenon.