The expression of P2Yß purinoceptor in muscle : the functional role in the regulation of acetylcholinesterase and acetylcholine receptors

Abstract

In vertebrate neuromuscular junctions, adenosine 5'-triphosphate (ATP) is present at the motor nerve terminals, and is co-released with acetylcholine (ACh) during synaptic stimulation. Here, we provide several lines of evidence which suggest that the synaptic ATP could act as a synapse-organizing factor to induce the expression of acetylcholinesterase (AChE) and acetylcholine receptor (AChR) in muscles. The induction of AChE and AChR α-subunit gene expression is mediated by one of the subtypes of ATP receptors, namely P2Y₁ purinoceptor. The binding characteristics of [³⁵S]dATPαS on chick muscle membranes resembled to P2Y₁ purinoceptors. The activation of P2Y₁ purinoceptor, when challenged with agonists, stimulated the accumulation of inositol 1, 4, 5-triphosphates (IP₃) and the mobilization of calcium in cultured chick myotubes. The transcript encoding P2Y₁ purinoceptor at ~3.2 kb was regulated in chick and rat muscle during development, denervation, regeneration after nerve injury and exercise. The P2Y₁ purinoceptor was co-localized with AChR in neuromuscular junction. Lastly, the expression of transcripts encoding AChE and AChR α-subunit was induced when the P2Y₁ purinoceptors were activated by specific agonists or by over-expression of P2Y₁ purinoceptors in cultured myotubes. These results provided direct evidence to support the novel function of ATP in directing the post-synaptic gene expression.

Date of Award	2000
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology