EFFECT OF ADENOSINE ON PHORBOL-MYRISTATE ACETATE INDUCED-REACTIVE OXYGEN METABOLITE PRODUCTION IN CULTURED MESANGIAL CELLS

Cultured rat mesangial cells produced chemiluminescence in response to phorbol myristate acetate. Because 90% of this chemiluminescence was suppressed by 10 mU/ml superoxide dismutase, reactive oxygen metabolit es are most likely involved in the chemiluminescence reaction. To clar ify the role of cyclic AMP in the regulation of reactive oxygen metabo lites production in cultured mesangial cells, we studied the effects o f adenosine, an adenosine analog (2-chloroadenosine), and forskolin on phorbol myristate acetate-induced chemiluminescence. Exogenous adenos ine suppressed the production of reactive oxygen metabolites in a dose -dependent manner (maximum at 1 mM adenosine: 70.6 +/- 3.2% of control ). Lower concentrations of 2-chloroadenosine (maximum at 100 mu M 2-ch loroadenosine: 63.2 +/- 2.1% of control) and forskolin (maximum at 200 mu M forskolin: 53.4 +/- 2.6% of control) also significantly suppress ed the production of reactive oxygen metabolites. In addition, adenosi ne analogs increased intracellular cyclic AMP in a dose-dependent mann er in the order: enosine)2-chloroadenosine)N-6-cyclohexyladenosine. Th ese results are in accordance with the probability that exogenous aden osine, by increasing intracellular cyclic AMP via the A2 receptor, inh ibits the production of reactive oxygen metabolites through direct pro tein kinase C activation induced by phorbol myristate acetate in cultu red rat mesangial cells.