title: Differing temporal roles of Ca2+ and cAMP in nicotine-elicited elevation of tyrosine hydroxylase mRNA.
abstract: The involvement of cAMP- and Ca2+-mediated pathways in the activation of tyrosine hydroxylase (TH) gene expression by nicotine was examined in PC-12 cells. Extracellular Ca2+ and elevations in intracellular Ca2+ concentration ([Ca2+]i) were required for nicotine to increase TH mRNA. The nicotine-elicited rapid rise in [Ca2+]i was inhibited by blockers of either L-type or N-type, and to a lesser extent P/Q-, but not T-type, voltage-gated Ca2+ channels. With continual nicotine treatment, [Ca2+]i returned to basal levels within 3-4 min. After a lag of approximately 5-10 min, there was a smaller elevation in [Ca2+]i that persisted for 6 h and displayed different responsiveness to Ca2+ channel blockers. This second phase of elevated [Ca2+]i was blocked by an inhibitor of store-operated Ca2+ channels, consistent with the observed generation of inositol trisphosphate. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM (BAPTA-AM), when added before or 2 h after nicotine, prevented elevation of TH mRNA. Nicotine treatment significantly raised cAMP levels. Addition of the adenylyl cyclase inhibitor 2', 5'-dideoxyadenosine (DDA) prevented the nicotine-elicited phosphorylation of cAMP response element binding protein. DDA also blocked the elevation of TH mRNA only when added after the initial transient rise in [Ca2+]i and not after 1 h. This study reveals that several temporal phases are involved in the induction of TH gene expression by nicotine, each of them with differing requirements for Ca2+ and cAMP.
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: V D
authors.initials: VD
authors.lastname: Gueorguiev
authors.forename: R J
authors.initials: RJ
authors.lastname: Zeman
authors.forename: B
authors.initials: B
authors.lastname: Hiremagalur
authors.forename: A
authors.initials: A
authors.lastname: Menezes
authors.forename: E L
authors.initials: EL
authors.lastname: Sabban
mesh_terms: D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology*; D007425:Intracellular Membranes / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009994:Osmolar Concentration; D016716:PC12 Cells; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
chemical_list: D015220:Calcium Channels; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D009538:Nicotine; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D000262:Adenylyl Cyclases; D002118:Calcium