CYCLIC-AMP MEDIATES THE PROSTAGLANDIN E(2)-INDUCED POTENTIATION OF BRADYKININ EXCITATION IN RAT SENSORY NEURONS

Prostaglandins enhance the sensitivity of sensory neurons to excitatory chemical agents, such as bradykinin. The intracellular transduction cascades mediating this potentiation remain largely unknown. We have examined the role of cyclic AMP in the prostaglandin E(2)-induced potentiation of sensory neurons. Pretreatment with agents that elevate intracellular cyclic AMP levels enhances the number of action potentials elicited by bradykinin. in a manner analogous to that of prostaglandin E(2). The prostaglandin E(2)-induced potentiation of the number of bradykinin-elicited action potentials is blocked by either inhibition of adenylyl cyclase or protein kinase A. Therefore, our results suggest that prostaglandin E(2) activates adenylyl cyclase to increase intracellular cyclic AMP, which in turn activates protein kinase A. Presumably activation of protein kinase A leads to increased levels of protein phosphorylation that then contribute to the enhancement of neuronal sensitivity to excitatory chemical agents.