PGE(2)-mediated inhibition of T cell p59(fyn) is independent of cAMP

We recently observed that prostaglandin E-2 (PGE(2))-mediated suppression o f T cell functions could result from an attenuation of p59(fyn) protein tyr osine kinase activity. The present study evaluated the effects of an adenyl ate cyclase agonist (forskolin) and antagonist (SQ-22536), as well as those of cAMP analogues (dibutyryl cAMP and 8-bromo- cAMP), on T cell p59(fyn) k inase activity. The study allowed us to assess whether PGE(2)-mediated acti vation of adenylate cyclase by itself or the elevation in intracellular cAM P levels is an integral event in the modulation of anti-CD3-linked p59(fyn) activation in T cells. The experiments were carried out with splenic T cel ls from male Sprague-Dawley rats. A 30-50% suppression in the autophosphory lation and the kinase activity of p59(fyn) in T cells incubated with PGE(2) or forskolin was observed. Pretreatment of T cells with SQ-22536 prevented significant PGE(2)-mediated inhibition of T cell p59(fyn) kinase activity. In contrast, no change in p59(fyn) autophosphorylation and kinase activity in T cells treated with cAMP analogues was observed. These data suggest th at PGE(2)-mediated suppression of p59(fyn) autophosphorylation and kinase a ctivity in T cells is dependent on the activation of adenylate cyclase and independent of the elevation in cAMP levels.