Effect of amyloid peptides on the increase in TrkA receptor expression induced by nicotine in vitro and in vivo.

Abstract

The ability of nicotine to induce a cytoprotective or neuroprotective action occurs through several downstream mechanisms. One possibility is that the drug increases the expression of tyrosine kinase A (TrkA) nerve growth factor (NGF) receptors. Certain beta-amyloid peptides (e.g., Abeta1-42) have been shown to bind with high affinity to alpha7 nicotinic receptors and thus interfere with a potentially neurotrophic influence. Treatment of differentiated PC-12 cells with nicotine produced a concentration-dependent increase in cell-surface TrkA receptors that occurred concomitantly with cytoprotection. The effect of nicotine was blocked by either of the alpha7 receptor antagonists alpha-bungarotoxin (alpha-BTX) or methyllycaconatine. The cytoprotective action of nicotine also was inhibited by pretreatment with 10-100 nM Abeta1-42. Nicotine also was administered (four injections of 30 microg, spaced evenly over 24 h) to rats by direct injection into a lateral cerebral ventricle. Brain TrkA expression was increased significantly in hippocampus and entorhinal cortex (up to 32% above control), with no changes found in cerebral cortex or hypothalamus. The nicotine-induced increases in TrKA expression in hippocampus and entorhinal cortex were significantly inhibited by 10 microg alpha-BTXor by 10 nmol Abeta1-42. Therefore, physiologically relevant concentrations of Abeta1-42 can prevent nicotine-induced TrkA receptor expression in brain regions containing cholinergic neurons susceptible to the neurotoxicity associated with Alzheimer's disease.

• Authors: Xinyu D Li, Esperanza Arias, Ramamohana R Jonnala, Shyamala Mruthinti, Jerry J Buccafusco
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 27 Issue 3 Pg. 325-36 ( 2005) ISSN: 0895-8696 [Print] United States
• PMID: 16280603 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Amyloid beta-Peptides
• Bungarotoxins
• Chrna7 protein, rat
• Neuroprotective Agents
• Nicotinic Agonists
• Nicotinic Antagonists
• Peptide Fragments
• Receptors, Nicotinic
• alpha7 Nicotinic Acetylcholine Receptor
• amyloid beta-protein (1-42)
• methyllycaconitine
• Nicotine
• Nerve Growth Factor
• Receptor, trkA
• Aconitine

Topics

• Aconitine (analogs & derivatives, metabolism, pharmacology)
• Amyloid beta-Peptides (metabolism, pharmacology)
• Animals
• Brain (anatomy & histology, drug effects, metabolism)
• Bungarotoxins (metabolism, pharmacology)
• Dose-Response Relationship, Drug
• Male
• Nerve Growth Factor (metabolism)
• Neuroprotective Agents (metabolism, pharmacology)
• Nicotine (pharmacology)
• Nicotinic Agonists (metabolism, pharmacology)
• Nicotinic Antagonists (metabolism, pharmacology)
• PC12 Cells
• Peptide Fragments (metabolism, pharmacology)
• Rats
• Rats, Wistar
• Receptor, trkA (metabolism)
• Receptors, Nicotinic (metabolism)
• alpha7 Nicotinic Acetylcholine Receptor