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.
Carter
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DA
Neuropeptide Laboratory, National University of Singapore, Kent Ridge.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D009924:Organ Culture Techniques; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides
D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D013449:Sulfonamides; D005576:Colforsin; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine