Objective The glial cells of the central nervous system are involved in tripartite signaling,therefore we have been investigating the relationship between sensory neurons and non-neuronal cells in isolated preparations of dorsal root ganglia(DRG).Methods The mixed cell cultures of dissociated DRG cells were separated to yield enriched fractions of IB4-positive cells(small diameter,non-peptidergic cells),IB4-negative cells(small diameter,peptidergic cells,and large diameter cells),and non-neuronal cells(principally satellite glial cells,Schwann cells and fibroblasts).Adenylyl cyclase activity was assayed by measuring production of [3H]cAMP from cells preloaded with [3H]adenine.Results PGE2 and the PGI2 mimetic cicaprost stimulated adenylyl cyclase activity which was inhibited by ONO-AE3-208(EP4 antagonist)or CAY10441(IP antagonist)with estimated pA2 values of 8.9 and 8.2,respectively.Surprisingly,both PGE2 and cicaprost-stimulated [3H] cAMP production was greatest in the non-neuronal cell preparation.Furthermore,when the number of non-neuronal cells was kept constant and the number of neuronal cells was increased,we observed a progressive decrease in prostanoid-stimulated activity.Conclusions Sensory neurons appear to regulate prostanoid receptor-mediated cell signaling in non-neuronal cells within the DRG. Objective The glial cells of the central nervous system are involved in tripartite signaling, therefore we have been investigating the relationship between sensory neurons and non-neuronal cells in isolated preparations of dorsal root ganglia (DRG). Methods The mixed cell cultures of dissociated DRG cells were separated to yield enriched fractions of IB4-positive cells (small diameter, non-peptidergic cells), IB4 negative cells (small diameter, peptidergic cells, and large diameter cells), and non-neuronal cells (principally satellite glial cells, Schwann cells and fibroblasts. Adenylyl cyclase activity was assayed by measuring production of [3H] cAMP from cells preloaded with [3H] adenine. Results PGE2 and the PGI2 mimetic cicaprost stimulated adenylyl cyclase activity which was inhibited by ONO-AE3-208 (EP4 antagonist ) or CAY10441 (IP antagonist) with estimated pA2 values ​​of 8.9 and 8.2, respectively. Both pGE2 and cicaprost-stimulated [3H] cAMP production was greatest in the non-neuronal ce ll preparation. Future plus, when the number of non-neuronal cells was kept constant and the number of neuronal cells was increased, we observed a progressive decrease in prostanoid-stimulated activity. Confins Sensory neurons appear to regulate prostanoid receptor-mediated cell signaling in non -neuronal cells within the DRG.