title: Rhythmic expression of adenylyl cyclase VI contributes to the differential regulation of serotonin N-acetyltransferase by bradykinin in rat pineal glands.
abstract: The rhythmic nocturnal production of melatonin in pineal glands is controlled by the periodic release of norepinephrine from the superior cervical ganglion. Norepinephrine binds to the beta-adrenergic receptor and stimulates an increase in intracellular cAMP levels, leading to the transcriptional activation of serotonin N-acetyltransferase, which in turn promotes melatonin production. In the present study, we report that bradykinin inhibits basal- and forskolin-stimulated adenylyl cyclase activity, norepinephrine-induced cAMP generation, and N-acetyltransferase expression in a calcium-dependent manner. These effects were blocked by pretreatment with U73122 (a selective phospholipase C inhibitor), and 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (a Ca(2+) chelator), but not pertussis toxin. The calcium ionophore, ionomycin, inhibited isoproterenol-mediated cAMP generation, similar to bradykinin. Interestingly, the inhibitory effect of bradykinin was evident only during the daytime. At midday, bradykinin inhibited the cAMP level by approximately 50% but markedly stimulated cAMP production (by approximately 50%) at night. Northern blotting and immunoblotting data disclosed circadian expression of calcium-inhibitable adenylyl cyclase type 6. Expression of adenylyl cyclase type 6 was maximal at Zeitgeber Time (ZT) 01 and very low at ZT 13. Our results suggest that bradykinin-induced calcium inhibits melatonin synthesis through the mediation of adenylyl cyclase type 6 expression.
authors.affiliation: System Bio-Dynamics NCRC, Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang 790-784, Republic of Korea.
authors.forename: Sung
authors.initials: S
authors.lastname: Han
authors.forename: Tae-Don
authors.initials: TD
authors.lastname: Kim
authors.forename: Dae-Cheong
authors.initials: DC
authors.lastname: Ha
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
mesh_terms: D000262:Adenylyl Cyclases / Q000096:biosynthesis* / Q000502:physiology*; D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000378:metabolism; D015152:Blotting, Northern; D001920:Bradykinin / Q000502:physiology*; D002118:Calcium / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D002940:Circadian Rhythm; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D016257:Fura-2 / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D015151:Immunoblotting; D015544:Inositol 1,4,5-Trisphosphate / Q000737:chemistry; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007545:Isoproterenol / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010870:Pineal Gland / Q000166:cytology / Q000378:metabolism*; D020033:Protein Isoforms; D011760:Pyrrolidinones / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D017783:Superior Cervical Ganglion / Q000378:metabolism; D013997:Time Factors; D015533:Transcriptional Activation; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: D002614:Chelating Agents; D004791:Enzyme Inhibitors; D004963:Estrenes; D005456:Fluorescent Dyes; D007476:Ionophores; D010726:Phosphodiesterase Inhibitors; D020033:Protein Isoforms; D011760:Pyrrolidinones; D012333:RNA, Messenger; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D005576:Colforsin; D004533:Egtazic Acid; D015759:Ionomycin; D012313:RNA; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D047068:Arylalkylamine N-Acetyltransferase; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; C121100:adenylyl cyclase 6; D008550:Melatonin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D007545:Isoproterenol; D001920:Bradykinin; D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine