The cellular mechanisms by which opioid and general anaesthetic drugs produce their clinical effect remain unclear, but modulation of stimulus-secretion coupling may be important. The human neuroblastoma cell line, SH-SY5Y, is a model of a human sympathetic neuron. The uptake and release (depolarization and receptor mediated) of [3H] noradrenaline ([3H] NA) in SH-SY5Y cells has been characterized, and the role of cAMP and calcium in evoked release examined. Further studies examined the effect of opioids (including fentanyl), a volatile anaesthetic agent (halothane), and intravenous anaesthetics (thiopentone and propofol) on uptake and release of [3H] NA. SH-SY5Y cells are capable of the uptake and evoked release of [3H] NA. K+ evoked release is dependent on extracellular calcium but carbachol evoked release appears to be extracellular calcium- independent. cAMP does not have a role in the immediate evoked release of [3H] NA, but an effect on long term secretion cannot be excluded. Fentanyl inhibits the uptake and release of [3H] NA, but this effect is not opiate receptor mediated. Morphine, DAMGO, met- and leu- enkephalin had no effect on [3H] NA release, and these results indicate that opiate receptors on SH-SY5Y cells are not coupled to neurotransmitter release. Halothane inhibits K+, but not carbachol evoked [3H] NA release. In addition, halothane inhibits [3H] NA uptake but only at relatively high concentrations. Thiopentone, but not propofol, inhibits [3H] NA uptake, and both drugs inhibit [3H] NA release. The results of these studies suggest that inhibition of voltage sensitive calcium channels by general anaesthetic agents may contribute significantly towards the state of anaesthesia.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:674316 |
| Date | January 1994 |
| Creators | Atcheson, Robert |
| Publisher | University of Leicester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/2381/33637 |
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