REGULATION OF THE EXPRESSION OF THE PROENKEPHALIN GENE IN CULTURED MENINGEAL FIBROBLASTS - OPPOSITE EFFECTS OF ALPHA(1)-ADRENOCEPTOR AND BETA(2)-ADRENOCEPTOR

Meningeal fibroblasts express the proenkephalin gene during embryonal development but terminate the expression shortly before birth. When br ought into primary culture at postnatal day 1, the fibroblasts again e xpress the gene. Activation of protein kinase A reduces this expressio n and thus may contribute to its prenatal termination. Since the norad renergic innervation of the meninges bes gins around the time of birth , it was investigated in the present study, how adrenergic agonists af fected the levels of proenkephalin mRNA in cultured fibroblasts. The b eta(2)-adrenoceptor agonists salbutamol and procaterol increased the l evels of endogenous cAMP and diminished the concentration of proenkeph alin mRNA indicating that the cultured fibroblasts possessed this beta -subtype, In contrast, noradrenaline increased the level of proenkepha lin mRNA in a concentration-dependent manner. This effect was independ ent of endogenous cAMP and was mediated by alpha(1)-adrenoceptors. The data indicate that the noradrenergic ins nervation of the meninges at the time of birth is not responsible for the termination of the proen kephalin gene expression.