Prostaglandin D2 modulates calcium signals induced by prostaglandin E2 in neurons of rat dorsal root ganglia

Fever in response to a localized subcutaneous stimulation with a low dose of lipopolysaccharide (LPS) can be attenuated by co-administration of a local anesthetic or the non-selective cyclooxygenase (COX) inhibitor diclofenac at doses, which do not exert systemic effects when injected at sites remote from the area of inflammatory stimulation. These results suggest a participation of neuronal afferent signals mediated by COX-products in the manifestation of fever under these conditions. We therefore, measured intracellular Ca2+-concentrations in cultured neurons from rat dorsal root ganglia (DRG) stimulated with the pyrogenic mediator prostaglandin E-2 (PGE(2)), the anti-inflammatory and antipyretic mediator PGD(2), mixtures of both PGs, and menthol using the fura-2 ratio imaging technique. Neurons could be grouped according to their size with diameters of about 15 mu m (small), 35 mu m (medium sized), or 55 mu m (large). 96 out of 264 neurons responded to PGE(2) with pronounced Ca2+-signals, 53 of them being also responsive to menthol, indicative of their function as cold-sensors. 80% of these neurons belonged to the medium sized group. In a next experiment, we tested whether Ca2+-signals of PGE(2) responsive neurons were modulated by PGD(2). In 60% of all neurons investigated (n = 57), the strength of the PGE(2)-induced Ca2+-signals was reduced by co-administration of PGD(2). This effect was also observed in those neurons that were responsive to PGE(2) and menthol (n = 23; p < 0.001). This observation indicates antagonistic effects of PGE(2) and PGD(2) on a neuronal pathway that involves cold sensors and is activated during a localized subcutaneous inflammation. This finding might provide an explanation for the reported antipyretic and anti-inflammatory capacities of PGD(2). (C) 2015 Elsevier Ireland Ltd. All rights reserved.