Twenty-four hour exposure to prostaglandin downregulates prostanoid receptor binding but does not alter PGE(2)-mediated sensitization of rat sensory neurons.

Although the tissue levels of prostaglandins are elevated for a relatively long period during injury or inflammation, few studies have been performed to assess the effects of prolonged prostaglandin exposure on receptor binding and activity in sensory neurons. Consequently, we examined whether unilateral inflammation or a 24 h exposure to prostaglandin E2 (PGE2) altered binding of this prostanoid in spinal cord tissue or in isolated sensory neurons, respectively. To assess functional changes in EP receptors, we also examined PGE2-induced cAMP production and the prostanoid-mediated augmentation of substance P release from isolated sensory neurons after acute and 24 h pretreatment with PGE2. Injection of complete Freund's adjuvant into the hindpaw decreased binding of PGE2 in ipsilateral, but not contralateral dorsal spinal cord 24 h after injection. This decrease in Bmax was blocked by administration of intrathecal ketorolac (10 nmol/microl/h) for 24 h prior to and throughout the period of inflammation, suggesting that the inflammation-induced decrease in binding is dependent on prostaglandin synthesis. In an analogous manner, treating sensory neurons grown in culture with 1 microM PGE2 for 24 h decreased [3H]-PGE2 binding by approximately 50% without altering binding affinity. Exposing neuronal cultures to 1 microM PGE2 for 24 h also reduced, but did not abolish the ability of the prostanoid to increase the production of cAMP. This treatment, however, did not significantly alter the ability of PGE2 to augment the evoked release of immunoreactive substance P from sensory neurons. These results demonstrate that under conditions that significantly downregulate PGE2 binding, sensory neurons are still capable of maintaining PGE2-mediated sensitization.