PMID- 10535767 OWN - NLM STAT- MEDLINE DCOM- 19991117 LR - 20190921 IS - 0742-3098 (Print) IS - 0742-3098 (Linking) VI - 27 IP - 3 DP - 1999 Oct TI - CREB phosphorylation and melatonin biosynthesis in the rat pineal gland: involvement of cyclic AMP dependent protein kinase type II. PG - 170-82 AB - Phosphorylation of cyclic AMP response element binding protein (CREB) at amino acid serine 133 appears as an important link between the norepinephrine (NE)-induced activation of second messenger systems and the stimulation of melatonin biosynthesis. Here we investigated in the rat pineal gland: 1) the type of protein kinase that mediates CREB phosphorylation: and 2) its impact on melatonin biosynthesis. Immunochemical or immunocytochemical demonstration of serine133-phosphorylated cyclic AMP regulated element binding protein (pCREB) and radioimmunological detection of melatonin revealed that only cyclic AMP-dependent protein kinase (PKA) inhibitors suppressed NE-induced CREB phosphorylation and stimulation of melatonin biosynthesis, whereas inhibitors of cyclic GMP-dependent protein kinase (PKG), mitogen-activated protein kinase kinase, protein kinase C, or calcium-calmodulin-dependent protein kinase (CaMK) were ineffective. Investigations with cyclic AMP-agonist pairs that selectively activate either PKA type I or II link NE-induced CREB phosphorylation and stimulation of melatonin biosynthesis to the activation of PKA type II. Our data suggest that PKA type II plays an important role in the transcriptional control of melatonin biosynthesis in the rat pineal organ. FAU - Maronde, E AU - Maronde E AD - Dr. Senckenbergische Anatomie, Anatomisches Institut II, J.W. Goethe Universitat, Frankfurt, FRG. FAU - Wicht, H AU - Wicht H FAU - Tasken, K AU - Tasken K FAU - Genieser, H G AU - Genieser HG FAU - Dehghani, F AU - Dehghani F FAU - Olcese, J AU - Olcese J FAU - Korf, H W AU - Korf HW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Pineal Res JT - Journal of pineal research JID - 8504412 RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Enzyme Inhibitors) RN - 0 (Protein Kinase Inhibitors) RN - 17885-08-4 (Phosphoserine) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinase Type II) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - JL5DK93RCL (Melatonin) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Animals MH - Cell Nucleus/enzymology MH - Cyclic AMP Response Element-Binding Protein/analysis/*metabolism MH - Cyclic AMP-Dependent Protein Kinase Type II MH - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/*metabolism MH - Enzyme Inhibitors/pharmacology MH - Immunohistochemistry MH - Male MH - Melatonin/*biosynthesis MH - Norepinephrine/pharmacology MH - Phosphorylation MH - Phosphoserine/analysis/metabolism MH - Pineal Gland/chemistry/drug effects/*metabolism MH - Protein Kinase Inhibitors MH - Rats MH - Rats, Wistar EDAT- 1999/10/27 00:00 MHDA- 1999/10/27 00:01 CRDT- 1999/10/27 00:00 PHST- 1999/10/27 00:00 [pubmed] PHST- 1999/10/27 00:01 [medline] PHST- 1999/10/27 00:00 [entrez] AID - 10.1111/j.1600-079x.1999.tb00613.x [doi] PST - ppublish SO - J Pineal Res. 1999 Oct;27(3):170-82. doi: 10.1111/j.1600-079x.1999.tb00613.x.