Expression and regulation of kappa opiate receptors in rat spinal cord-dorsal root ganglion cocultures.

We have been using rat spinal cord-dorsal root ganglion primary cocultures (SC-DG) as a model system for exploring K receptor regulation. During the first 10 days in culture, the total number of opiate receptors increased markedly, reaching a Bmax of 180 fmoles/mg protein for K sites and a Bmax of 50 fmoles/mg protein for mu sites. Following this period of development, the K and mu receptor number did not change significantly. No detectable delta sites were observed at any time of culture. The binding of [3H]diprenorphine to K sites was found to be saturable, of high affinity and stereospecific. After chronic agonist treatment of cultured cells, K receptors did not down-regulate, whereas more than 50% of the mu receptor sites did. Following chronic antagonist treatment, mu receptors were markedly up-regulated (260% of control), while K sites exhibited a weaker up-regulation response (160% of control). These data demonstrate that K opiate receptors are expressed at high concentrations in SC-DG cultures and that contrary to mu receptors in spinal cord and delta receptors in NG10815 cells, K binding sites are less susceptible to modulation following chronic agonist or antagonist treatment. This suggests that K receptors may be regulated by different control mechanisms.