Nicotine‐induced phosphorylation of extracellular signal‐regulated protein kinase and CREB in PC12h cells

We have investigated mechanisms of nicotine‐induced phosphorylation of extracellular signal‐regulated protein kinase (p42/44 MAP kinase, ERK) and cAMP response element binding protein (CREB) in PC12h cells. Nicotine transiently induced ERK phosphorylation at more than 1 µm. The maximal level of nicotine‐induced ERK phosphorylation was lower than that of the membrane depolarization induced and, to a great extent, the nerve growth factor (NGF)‐induced ERK phosphorylation. Nicotinic acetylcholine receptor (nAChR) α7 subunit‐selective inhibitors had no significant effect on nicotine‐induced ERK phosphorylation. l‐Type voltage‐sensitive calcium channel antagonists inhibited nicotine‐induced ERK phosphorylation. Calcium imaging experiments showed that α7‐containing nAChR subtypes were functional at 1 µm of nicotine in the nicotine‐induced calcium influx, and non‐α7 nAChRs were prominent in the Ca2+ influx at 50 µm of nicotine. An expression of dominant inhibitory Ras inhibited nicotine‐induced ERK phosphorylation. A calmodulin antagonist, a CaM kinase inhibitor, a MAP kinase kinase inhibitor inhibited nicotine‐induced ERK and CREB phosphorylation. The time course of the phosphorylation of CREB induced by nicotine was similar to that of ERK induced by nicotine. These results suggest that non‐α7 nAChRs are involved in nicotine‐induced ERK phosphorylation through CaM kinase and the Ras‐MAP kinase cascade and most of the nicotine‐induced CREB phosphorylation is mediated by the ERK phosphorylation in PC12h cells.

[1]  Eric J. Nestler,et al.  Molecular basis of long-term plasticity underlying addiction , 2001, Nature Reviews Neuroscience.

[2]  Mu-ming Poo,et al.  The neurotrophin hypothesis for synaptic plasticity , 2000, Trends in Neurosciences.

[3]  E. Meyer,et al.  Involvement of α7 Nicotinic Acetylcholine Receptors in Activation of Tyrosine Hydroxylase and Dopamine β‐Hydroxylase Gene Expression in PC12 Cells , 2000 .

[4]  T. Ikeuchi,et al.  Regulation of α3 Nicotinic Acetylcholine Receptor Subunit mRNA Levels by Nerve Growth Factor and Cyclic AMP in PC12 Cells , 2000, Journal of neurochemistry.

[5]  I. Parnas,et al.  Autoreceptors, membrane potential and the regulation of transmitter release , 2000, Trends in Neurosciences.

[6]  T. Soderling,et al.  Postsynaptic protein phosphorylation and LTP , 2000, Trends in Neurosciences.

[7]  H. Kawakami,et al.  Effects of nerve growth factor and nicotine on the expression of nicotinic acetylcholine receptor subunits in PC12 cells , 1999, Neuroscience Research.

[8]  A. Ullrich,et al.  Distinct Calcium-dependent Pathways of Epidermal Growth Factor Receptor Transactivation and PYK2 Tyrosine Phosphorylation in PC12 Cells* , 1999, The Journal of Biological Chemistry.

[9]  D. K. Berg,et al.  Nicotinic Acetylcholine Receptors Containing ␣7 Subunits Are Required for Reliable Synaptic Transmission in Situ , 1999 .

[10]  D. Storm,et al.  Making New Connections Role of ERK/MAP Kinase Signaling in Neuronal Plasticity , 1999, Neuron.

[11]  J. Comella,et al.  Calcium Influx Activates Extracellular-regulated Kinase/Mitogen-activated Protein Kinase Pathway through a Calmodulin-sensitive Mechanism in PC12 Cells* , 1999, The Journal of Biological Chemistry.

[12]  T. Dunwiddie,et al.  Synaptic Potentials Mediated via α-Bungarotoxin-Sensitive Nicotinic Acetylcholine Receptors in Rat Hippocampal Interneurons , 1998, The Journal of Neuroscience.

[13]  Scott T. Wong,et al.  Cross Talk between ERK and PKA Is Required for Ca2+ Stimulation of CREB-Dependent Transcription and ERK Nuclear Translocation , 1998, Neuron.

[14]  E. Levin,et al.  Nicotinic acetylcholine involvement in cognitive function in animals , 1998, Psychopharmacology.

[15]  F. Hobbs,et al.  Identification of a Novel Inhibitor of Mitogen-activated Protein Kinase Kinase* , 1998, The Journal of Biological Chemistry.

[16]  D. O'Connor,et al.  A crucial role for the mitogen-activated protein kinase pathway in nicotinic cholinergic signaling to secretory protein transcription in pheochromocytoma cells. , 1998, Molecular pharmacology.

[17]  J. Changeux,et al.  Brain nicotinic receptors: structure and regulation, role in learning and reinforcement 1 Published on the World Wide Web on 24 October 1997. 1 , 1998, Brain Research Reviews.

[18]  Steven Finkbeiner,et al.  CREB: A Major Mediator of Neuronal Neurotrophin Responses , 1997, Neuron.

[19]  E. Ullian,et al.  Rapid Synaptic Transmission in the Avian Ciliary Ganglion Is Mediated by Two Distinct Classes of Nicotinic Receptors , 1997, The Journal of Neuroscience.

[20]  D. K. Berg,et al.  Detection of Functional Nicotinic Receptors Blocked by α-Bungarotoxin on PC12 Cells and Dependence of Their Expression on Post-Translational Events , 1997, The Journal of Neuroscience.

[21]  H. Ishiguro,et al.  Nicotine regulates mRNA level of tyrosine hydroxylase gene but not that of nicotinic acetylcholine receptor genes in PC12 cells , 1997, Neuroscience Letters.

[22]  J. S. Coggan,et al.  Synaptic Currents Generated by Neuronal Acetylcholine Receptors Sensitive to α-Bungarotoxin , 1996, Neuron.

[23]  R. Gray,et al.  Hippocampal synaptic transmission enhanced by low concentrations of nicotine , 1996, Nature.

[24]  K. Chergui,et al.  Nicotine injections into the ventral tegmental area increase locomotion and Fos-like immunoreactivity in the nucleus accumbens of the rat , 1996, Brain Research.

[25]  D. Bertrand,et al.  Neuronal nicotinic alpha 7 receptor expressed in Xenopus oocytes presents five putative binding sites for methyllycaconitine. , 1996, The Journal of physiology.

[26]  L. Role,et al.  Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors. , 1995, Science.

[27]  E. Peles,et al.  Protein tyrosine kinase PYK2 involved in Ca2+-induced regulation of ion channel and MAP kinase functions , 1995, Nature.

[28]  S. Matta,et al.  Nicotine regulates nicotinic cholinergic receptors and subunit mRNAs in PC 12 cells through protein kinase A. , 1995, Brain research. Molecular brain research.

[29]  B. Hiremagalur,et al.  Nicotine elicits changes in expression of adrenal catecholamine biosynthetic enzymes, neuropeptide Y and immediate early genes by injection but not continuous administration. , 1995, Brain research. Molecular brain research.

[30]  Thomas C. Südhof,et al.  The synaptic vesicle cycle: a cascade of protein–protein interactions , 1995, Nature.

[31]  J. Kononen,et al.  Neuronal regulation of c-fos, c-jun, and junB immediate-early genes in rat adrenal medulla , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  H. Heller,et al.  Nicotine administration differentially affects gene expression in the maternal and fetal circadian clock. , 1995, Brain research. Developmental brain research.

[33]  Jagdeepkaur Dani,et al.  Quantitative measurement of calcium flux through muscle and neuronal nicotinic acetylcholine receptors , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[34]  M. Greenberg,et al.  Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB , 1994, Cell.

[35]  M. Greenberg,et al.  Membrane depolarization and calcium influx stimulate MEK and MAP kinase via activation of Ras , 1994, Neuron.

[36]  A. Jayaraman,et al.  Nicotine induced c-fos expression in the striatum is mediated mostly by dopamine D1 receptor and is dependent on NMDA stimulation. , 1994, Brain research. Molecular brain research.

[37]  R. Maue,et al.  Nerve growth factor increases nicotinic ACh receptor gene expression and current density in wild-type and protein kinase A-deficient PC12 cells , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[38]  A. Jayaraman,et al.  Acute nicotine injections induce c-fos mostly in non-dopaminergic neurons of the midbrain of the rat. , 1993, Brain research. Molecular brain research.

[39]  T. Hökfelt,et al.  Differential expression of immediate early genes in the superior cervical ganglion after nicotine treatment , 1993, Neuroscience.

[40]  K. Malik,et al.  Alpha adrenergic receptor subtypes involved in prostaglandin synthesis are coupled to Ca++ channels through a pertussis toxin-sensitive guanine nucleotide-binding protein. , 1993, The Journal of pharmacology and experimental therapeutics.

[41]  S. Matta,et al.  Nicotine stimulates the expression of cFos protein in the parvocellular paraventricular nucleus and brainstem catecholaminergic regions. , 1993, Endocrinology.

[42]  M E Greenberg,et al.  Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways. , 1993, Science.

[43]  J. Patrick,et al.  Molecular cloning, functional properties, and distribution of rat brain alpha 7: a nicotinic cation channel highly permeable to calcium , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[44]  S. Heinemann,et al.  The expression of nicotinic acetylcholine receptors by PC12 cells treated with NGF , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[45]  D. Bertrand,et al.  Methyl lycaconitine: A novel nicotinic antagonist , 1992, Molecular and Cellular Neuroscience.

[46]  Zhong-Wei Zhang,et al.  Nicotinic receptors that bind α-bungarotoxin on neurons raise intracellular free ca2+ , 1992, Neuron.

[47]  M. Hagiwara,et al.  The newly synthesized selective Ca2+/calmodulin dependent protein kinase II inhibitor KN-93 reduces dopamine contents in PC12h cells. , 1991, Biochemical and biophysical research communications.

[48]  S. Sands,et al.  Calcium permeability of neuronal nicotinic acetylcholine receptor channels in PC12 cells , 1991, Brain Research.

[49]  M. Greenberg,et al.  CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases. , 1991, Science.

[50]  E. Kandel,et al.  cAMP response element-binding protein is activated by Ca2+/calmodulin- as well as cAMP-dependent protein kinase. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[51]  D. Bertrand,et al.  A neuronal nicotinic acetylcholine receptor subunit (α7) is developmentally regulated and forms a homo-oligomeric channel blocked by α-BTX , 1990, Neuron.

[52]  G. Cooper,et al.  Effect of a dominant inhibitory Ha-ras mutation on neuronal differentiation of PC12 cells , 1990, Molecular and cellular biology.

[53]  G. Lunt,et al.  Methyllycaconitine: a selective probe for neuronal α‐bungarotoxin binding sites , 1990 .

[54]  M. Greenberg,et al.  Stimulation of neuronal acetylcholine receptors induces rapid gene transcription. , 1986, Science.

[55]  A. Riccio,et al.  Spatial considerations for stimulus-dependent transcription in neurons. , 2000, Annual review of physiology.

[56]  A. Shaywitz,et al.  CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. , 1999, Annual review of biochemistry.

[57]  B. Hiremagalur,et al.  Differing temporal roles of Ca2+ and cAMP in nicotine-elicited elevation of tyrosine hydroxylase mRNA. , 1999, The American journal of physiology.

[58]  S. Arneric,et al.  The pharmacology of (-)-nicotine and novel cholinergic channel modulators. , 1997, Advances in pharmacology.

[59]  N. Benowitz.  Pharmacology of nicotine: addiction and therapeutics. , 1996, Annual review of pharmacology and toxicology.

[60]  J. Lindstrom,et al.  Affinity purification of nicotinic acetylcholine receptor from rat brain. , 1991, Advances in Experimental Medicine and Biology.

[61]  A. Drasdo,et al.  Presynaptic nicotinic receptors and the modulation of transmitter release. , 1990, Ciba Foundation symposium.

[62]  I. Stolerman.  Behavioural pharmacology of nicotine: implications for multiple brain nicotinic receptors. , 1990, Ciba Foundation symposium.

[63]  A. Wein,et al.  High-affinity, divalent ion-specific binding of 3H-ATP to homogenate derived from rabbit urinary bladder. Comparison with divalent-ion ATPase activity. , 1983, Molecular Pharmacology.