We have been studying the control of beta-adrenergic receptors (beta-AR) expression in rat C6 glioma cells. Beta-adrenergic receptors are members of the superfamily of G-protein linked receptors. Both beta1- and beta2-AR subtypes are present on C6 glioma cells. Both receptors, when occupied by agonist, stimulate the production of c-AMP. We have reported previously that the beta1- and beta2-AR mRNAs are differentially regulated when stimulated by agonist. We have since learned that both type and degree of mRNA changes induced by agonist stimulation are dependent on cell culture conditions and passage number. Preliminary evidence suggests that stimulation by agonist causes perturbations in total cellular protein and RNA synthesis which may be an important part of the mechanism by which these receptor mRNAs are regulated. We have also found that manipulation of the C6 glioma cell cytoarchtecture using drugs acting on microtubules discovered that serotonin and serotonin antagonists have the ability to down-regulate beta-AR mRNA in C6 glioma cells. In conjunction with the fact that several beta-AR antagonists bind with significant affinity and stereoselectivity to serotonin receptors, this may explain how beta-AR antagonists can by themselves cause down-regulation of beta-AR mRNA. The crosstalk between beta-adrenergic and serotoninergic receptors has interesting implications with regard to clinical depression, since both receptors have been pharmacologically indicated in this dysfunction. Finally, in collaboration with Dr. W. Potter's branch, we have found that treatment of C6 glioma cells with carbamazepine for 3 or more days induces a significant up-regulation of beta-AR mRNA. In view of the antidepressant effects of carbamazepine, this finding may also contribute to an understanding of depression.
