Cyclic AMP mediates the prostaglandin E2-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 E2-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 E2. The prostaglandin E2-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 E2 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.
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D015232:Dinoprostone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D008564:Membrane Potentials / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D015398:Signal Transduction / Q000502:physiology
D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone; D001920:Bradykinin