|
|
||||||||
Departments of 1 Biochemistry and Molecular Biology and 2 Cell Biology and Anatomy, New York Medical College, Valhalla, New York 10595
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 ~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.
adenylyl cyclase; voltage-gated calcium channels; adenosine 3',5'-cyclic monophosphate response element binding protein
This article has been cited by other articles:
![]() |
J. Oshikawa, Y. Toya, T. Fujita, M. Egawa, J. Kawabe, S. Umemura, and Y. Ishikawa Nicotinic acetylcholine receptor {alpha}7 regulates cAMP signal within lipid rafts Am J Physiol Cell Physiol, September 1, 2003; 285(3): C567 - C574. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. J. Dewar, B. U. Bradford, and R. G. Thurman Nicotine Increases Hepatic Oxygen Uptake in the Isolated Perfused Rat Liver by Inhibiting Glycolysis J. Pharmacol. Exp. Ther., June 1, 2002; 301(3): 930 - 937. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. B. Gauda, R. Cooper, P. K. Akins, and G. Wu Prenatal nicotine affects catecholamine gene expression in newborn rat carotid body and petrosal ganglion J Appl Physiol, November 1, 2001; 91(5): 2157 - 2165. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Venkatesh, G. Siddhartha, R. Joshi, S. Patel, and G. Hasan Interactions Between the Inositol 1,4,5-Trisphosphate and Cyclic AMP Signaling Pathways Regulate Larval Molting in Drosophila Genetics, May 1, 2001; 158(1): 309 - 318. [Abstract] [Full Text] |
||||
![]() |
J. B.Mailhes, D. Young, G. Caldito, and S.N. London Sensitivity of mouse oocytes to nicotine-induced perturbations during oocyte meiotic maturation and aneuploidy in vivo and in vitro Mol. Hum. Reprod., March 1, 2000; 6(3): 232 - 237. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |