Regulation of prostacyclin and prostaglandin E2 receptor mediated responses in adult rat dorsal root ganglion cells, in vitro

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Abstract
Primary cultures of adult rat dorsal root ganglia (DRG) were prepared to examine the properties of prostacyclin (IP) receptors and prostaglandin E2 (EP) receptors in sensory neurones. IP receptor agonists, cicaprost and iloprost, stimulated adenylyl cyclase activity with EC50 values of 22 and 28 nM, respectively. Prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2) were 7 fold less potent than cicaprost and iloprost, with PGE2 displaying a lower maximal response. Adenylyl cyclase activation by iloprost, PGE1 and PGE2, but not by forskolin, was highly dependent on DRG cell density. Although the potency of iloprost and PGE2 for stimulating adenylyl cyclase was unchanged, their maximal responses were significantly increased at low cell density. Both IP and EP2/4 receptors could be down‐regulated by agonist pretreatment, however the presence of cyclo‐oxygenase (COX) inhibitors did not prevent this apparent down‐regulation of IP and EP2/4 receptors at high DRG cell densities. Stimulation of adenylyl cyclase by the neuropeptide calcitonin gene‐related peptide was also decreased at high DRG cell density, whereas the responses to β‐adrenoceptor agonists were increased at high DRG cell density. Addition of nerve growth factor (NGF), or the addition of anti‐neurotrophin antibodies during the 5‐day culture of DRG cells, had no effect on IP receptor‐mediated responses. These results indicate that Gs‐coupled receptors involved in nociception are regulated in a variable manner in adult rat sensory neurones, and that this cell density‐dependent regulation may be agonist‐independent for IP and EP2/4 receptors. British Journal of Pharmacology (2001) 133, 13–22; doi:10.1038/sj.bjp.0704028

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