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

Prostaglandins enhance the sensitivity of sensory neurons to excitator y chemical agents, such as bradykinin. The intracellular transduction cascades mediating this potentiation remain largely unknown. We have e xamined the role of cyclic AMP in the prostaglandin E(2)-induced poten tiation of sensory neurons. Pretreatment with agents that elevate intr acellular cyclic AMP levels enhances the number of action potentials e licited by bradykinin. in a manner analogous to that of prostaglandin E(2). The prostaglandin E(2)-induced potentiation of the number of bra dykinin-elicited action potentials is blocked by either inhibition of adenylyl cyclase or protein kinase A. Therefore, our results suggest t hat prostaglandin E(2) activates adenylyl cyclase to increase intracel lular cyclic AMP, which in turn activates protein kinase A. Presumably activation of protein kinase A leads to increased levels of protein p hosphorylation that then contribute to the enhancement of neuronal sen sitivity to excitatory chemical agents.