Rhythmic expression of adenylyl cyclase VI contributes to the differential regulation of serotonin N-acetyltransferase by bradykinin in rat pineal glands.
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.
Han
Sung
S
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.
Kim
Tae-Don
TD
Ha
Dae-Cheong
DC
Kim
Kyong-Tai
KT
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
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