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Title: Purinergic signalling in mammalian skeletal muscle development and regeneration
Author: Ryten, Mina
ISNI:       0000 0001 3543 7980
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2003
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ATP is an important extracellular signalling molecule, mediating its effects by activation of P2X and P2Y receptors. Evidence for the presence of P2 receptors in skeletal muscle was first published over 15 years ago. However, the identities and functional significance of purinoceptors on skeletal muscle cells has remained unclear. Using a variety of techniques, purinoceptor subtype expression and function was studied. P2 receptors were detected during mammalian skeletal muscle development, regeneration in vivo and regeneration in vitro. In all cases, the purinoceptor subtypes expressed, and the timing and pattern of receptor expression were similar. Whereas the P2X5 and P2Y1 receptors were detected early in muscle formation, suggesting that purinergic signalling might regulate myoblast activity, coexpression of the P2X2 receptor and AChRs on myotubes suggested the involvement of this receptor in the regulation of AChR activation and localisation. The functional significance of P2 receptor expression on myoblasts was studied using primary cultures of rat skeletal muscle satellite cells. Application of ATP shifted the balance between proliferation and differentiation of satellite cells: exposing cells to ATP reduced the rate of proliferation, but increased levels of myogenin and p21 mRNA expression. Application of ATP also increased the expression of myosin heavy chain and the rate of myotube formation. The pharmacology of these effects and characterisation of purinoceptor expression on satellite cells, demonstrated the involvement of a P2X5 receptor. This receptor mediated changes in satellite cell activity by activating the MAPK signalling system. Application of ATP to satellite cells caused a rapid and significant increase in the phosphorylation of MAPKs and inhibition of p38 phosphorylation specifically, blocked the effect of ATP on satellite cell number. Thus, this is one of the first studies to demonstrate the expression of P2 receptors on developing and regenerating skeletal muscle, and link specific P2 receptor subtypes to processes in muscle formation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available