This study investigated G-protein coupled receptor (GPCR) and receptor tyrosine kinase (RTK)-mediated signal transduction via phospholipase C (PLC). A transient elevation of intracellular [Ca2+] ([Ca2+]i) was identified in response to PDGF-BB. Despite the recruitment and phosphorylation of PLC-, the mechanism was apparently novel and Ins(1,4,5)P3-independent. Muscarinic M3 receptor-dependent Ins(1.4.5)P3 and Ca2+ signalling was biphasic, consisting of a peak and plateau. Both agonist-occupied receptors relied on capacitative Ca2+ influx triggered by intracellular Ca2+ store release for maximum elevation of [Ca2+]i and initiated intracellular Ca2+ release from the same thapsigargin and Ins(1,4,5)P3-sensitive intracellular store. This study demonstrated that activation of muscarinic M3 receptors abolished PDGF-mediated elevation of [Ca2+]i by depleting the intracellular store, whilst PDGF receptors inhibited subsequent muscarinic receptor-mediated elevation of [Ca2+]i, possibly by inhibition of PLC- isoform. Furthermore, a PDGF-mediated elevation of [Ca2+]i was also identified in differentiated SH-SY5Y cells and hippocampal neurons. Muscarinic M3 receptors, PDGF receptors and epidermal growth factor (EGF) receptors activated mitogen-activated protein (MAP) kinase in SH-SY5Y cells. However, only PDGF-mediated MAP kinase activation had a Ca2+-dependent component suggesting that PDGF-mediated Ca2+ signalling may play other roles and an understanding of these functions emphasises the need to understand the mechanism of [Ca2+]i regulation by growth factor receptors in neurons.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:696955 |
| Date | January 2001 |
| Creators | Wheldon, Lee Mark |
| Publisher | University of Leicester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/2381/29930 |
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