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

J Neurochem. 2001 Nov;79(3):489-98. doi: 10.1046/j.1471-4159.2001.00602.x.

Abstract

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 microM. 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) alpha7 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 alpha7-containing nAChR subtypes were functional at 1 microM of nicotine in the nicotine-induced calcium influx, and non-alpha7 nAChRs were prominent in the Ca(2+) influx at 50 microM 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-alpha7 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aconitine / analogs & derivatives*
  • Aconitine / pharmacology
  • Animals
  • Benzylamines / pharmacology
  • Bungarotoxins / metabolism
  • Bungarotoxins / pharmacology
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calmodulin / antagonists & inhibitors
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Hexamethonium / pharmacology
  • Insecticides / pharmacology
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / physiology
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • Nerve Growth Factor / pharmacology
  • Neurons / cytology
  • Neurons / metabolism*
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Nicotinic Antagonists / pharmacology
  • Nifedipine / pharmacology
  • PC12 Cells
  • Phosphorylation
  • Potassium / pharmacology
  • Rats
  • Receptors, Nicotinic / metabolism
  • Sulfonamides / pharmacology
  • Tubocurarine / pharmacology
  • ras Proteins / metabolism

Substances

  • Benzylamines
  • Bungarotoxins
  • Calcium Channel Blockers
  • Calmodulin
  • Cyclic AMP Response Element-Binding Protein
  • Enzyme Inhibitors
  • Insecticides
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • Sulfonamides
  • KN 93
  • methyllycaconitine
  • Hexamethonium
  • W 7
  • Nicotine
  • Nerve Growth Factor
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • ras Proteins
  • Nifedipine
  • Potassium
  • Calcium
  • Tubocurarine
  • Aconitine