The ‘serotonin/norepinephrine link’ beyond the β adrenoceptor

C 6 rat glioma cells were utilized as a model system to probe the ‘serotonin/norepinephrine link’ at the level of preproenkephalin (PPE) gene expression. The β adrenoceptor mediated increase in PPE mRNA was attenuated by the selective β 1 adrenoceptor antagonist metoprolol which blocked the isoproterenol induced cyclic AMP generation by 97%. The subtype nonspecific antagonist propranolol blocked both the isoproterenol induced increase in cyclic AMP and the increase in the PPE mRNA steady-state levels. Serotonin (5-HT) had no effect on the density of β adrenoceptors or their down-regulation by isoproterenol and did not alter the PPE gene expression in the absence of the β signal. However, 5-HT significantly deamplified the β signal mediated enhancement of the PPE mRNA thus indicating that the aminergic link occurs beyond the β adrenoceptor.