NORADRENALINE INCREASES THE EXPRESSION OF THE PROENKEPHALIN GENE IN CULTURED ASTROGLIAL CELLS BY ACTING ON BETA(1)-ADRENOCEPTOR AND ALPHA(1)-ADRENOCEPTOR

In primary culture, type I astroglial cells from neocortex of newborn rats express the proenkephalin gene. The glial cells are not homogeneo us but differ in their morphology; i.e., polygonal and process-bearing cells are found. Transcription of the proenkephalin gene is increased via protein kinase A upon stimulation with cyclic AMP (cAMP) analogue s. In the present study, how noradrenaline affected the expression of the proenkephalin gene in both cell types was investigated. Noradrenal ine enhanced the levels of proenkephalin mRNA in a concentration-depen dent manner. Experiments with subtype-selective antagonists suggested that beta(1)-adrenoceptors were involved. In situ hybridization showed that proen-kephalin mRNA was induced only in polygonal cells. Noradre naline also increased the levels of cAMP. However, concentrations of n oradrenaline that produced a maximal increase in cAMP caused only subm aximal elevations of proenkephalin mRNA. This discrepancy was explaine d by the finding that noradrenaline increased the expression of the pr oenkephalin gene also via alpha(1)-adrenoceptors. It is concluded that beta(1)- and alpha(1)-adrenoceptors can act in a synergistic manner o n the expression of the proenkephalin gene in astroglial cells.