Studies of receptors for dopamine and serotonin in novel cell lines

Two novel cell lines established from rat anterior pituitary tumor 7315a have been used as model systems for the study of 5-HT$\sb2$ and D2 receptors. P11 cells grow attached to tissue culture plates and express a high density of 5-HT$\sb2$ receptors. These receptors are coupled to the stimulation of phosphoinositide hydrolysis in a pertussis toxin insensitive manner. P11 cells were used to identify N-substituted derivatives of spiroperidol with a decreased affinity for 5-HT$\sb2$ receptors. In other experiments, exposure of P11 cells to 5-HT led to a decrease in the density of 5-HT$\sb2$ receptors in P11 cells and desensitization of 5-HT$\sb2$ mediated phosphoinositide hydrolysis. The time course of receptor down-regulation was similar to the time course of desensitization, suggesting that a decrease in receptor density may be mechanistically involved in the desensitization of 5-HT$\sb2$ receptors in these cells. A second cell line derived from cells dispersed from the 7315a tumor was designated SUP1. In contrast to P11 cells, SUP1 cells grow in suspension and retain several characteristics of lactotroph pituitary cells: SUP1 cells secrete prolactin and express dopamine D2 receptors. These receptors are negatively coupled to adenylyl cyclase activity and to prolactin secretion. Exposure of SUP1 cells to dopamine led to a time-dependent increase in the density of D2 receptors. Levels of D2 receptor mRNA in the cells were also increased. The effect of dopamine on receptor density was mediated by an interaction with D2 receptors, since it was blocked by spiroperidol and was mimicked by N-propylnorapomorphine. Desensitization of D2 receptor-mediated inhibition of adenylyl cyclase activity was not observed. Although agonists generally cause desensitization and down-regulation of receptors, it is possible that agonists upregulate D2 receptors in the anterior pituitary. These results suggest that P11 and SUP1 cells are useful model systems for studies of agonist-induced regulation of 5-HT$\sb2$ and D2 receptors. Future studies are expected to use these cell lines to elucidate mechanisms for the regulation of 5-HT$\sb2$ and D2 receptors