Noradrenergic regulation of c-jun expression in the rat pineal gland in culture: positive and negative components.

One component of the nocturnal changes in cellular immediate-early gene expression in the rat pineal gland is a decrease in c-jun expression, mediated through beta-adrenoceptors. An in vitro study of the intracellular mechanisms which control c-jun expression has now shown that a norepinephrine-induced increase in c-jun mRNA levels in organ-cultured pineals is differentially modulated by protein kinase inhibitors; N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004) potentiated the response; however, in the presence of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a significant decrease in c-jun mRNA was found. Treatment with HA-1004 alone elevated the level of c-jun mRNA, H-7 alone was without effect. Forskolin together with 3-isobutyl-1-methylxanthine suppressed c-jun, whereas phorbol 12,13-dibutyrate raised c-jun mRNA levels. The results demonstrate opposing pathways for c-jun regulation in the pineal gland, and indicate that the nocturnal attenuation of c-jun expression involves selective activation of a negative pathway which may be linked to cAMP.