Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vertebrate neuromuscular junctions, ATP is stored at the motor nerve terminals and is co-released with acetylcholine during neural stimulation. Here, we provide several lines of evidence that the synaptic ATP can act as a synapse-organizing factor to induce the expression of acetylcholinesterase (AChE) and acetylcholine receptor (AChR) in muscles, mediated by a metabotropic ATP receptor subtype, the P2Y(1) receptor. The activation of the P2Y(1) receptor by adenine nucleotides stimulated the accumulation of inositol phosphates and intracellular Ca(2+) mobilization in cultured chick myotubes. P2Y(1) receptor mRNA in chicken muscle is very abundant before hatching and again increases in the adult. The P2Y(1) receptor protein is shown to be restricted to the neuromuscular junctions and colocalized with AChRs in adult muscle (chicken, Xenopus, and rat) but not in the chick embryo. In chicks after hatching, this P2Y(1) localization develops over approximately 3 weeks. Denervation or crush of the motor nerve (in chicken or rat) caused up to 90% decrease in the muscle P2Y(1) transcript, which was restored on regeneration, whereas the AChR mRNA greatly increased. Last, mRNAs encoding the AChE catalytic subunit and the AChR alpha-subunit were induced when the P2Y(1) receptors were activated by specific agonists or by overexpression of P2Y(1) receptors in cultured myotubes; those agonists likewise induced the activity in the myotubes of promoter-reporter gene constructs for those subunits, actions that were blocked by a P2Y(1)-specific antagonist. These results provide evidence for a novel function of ATP in regulating the gene expression of those two postsynaptic effectors.
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PMID:Expression of the P2Y1 nucleotide receptor in chick muscle: its functional role in the regulation of acetylcholinesterase and acetylcholine receptor. 1171 56

Adenosine 5'-triphosphate (ATP) is an important trophic factor, which is co-stored and co-released at central and peripheral cholinergic synapses. The synaptic ATP induces post-synaptic gene transcription during the formation and maintenance of vertebrate neuromuscular junction (nmj) via a mitogen-activaton protein (MAP) kinase signaling pathway and subsequently activates acetylcholinesterase (AChE) and acetylcholine receptor (AChR) genes. However, the role of ATP in the central nervous system is still not clear. Primary culture of rat cortical neurons was used as a model system to study the biological functions of ATP in neuron-neuron synapses. During the differentiation of cultured cortical neurons, the protein levels of AChE and one of the ATP receptor subtypes, P2Y1 receptor, were increased. By using a human AChE promoter tagged with a luciferase-reporter gene, the transcriptional regulation of AChE gene by ATP could be monitored. The activation of P2Y1 receptors could regulate the AChE promoter activity in cultured cortical neurons. These results suggested the activation of P2Y receptors may play role(s) in synaptic gene expression of neuron-neuron synapses in the brain.
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PMID:ATP induces the post-synaptic gene expression in neuron-neuron synapses: Transcriptional regulation of AChE catalytic subunit. 1642 71