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Title: Opioids and anaesthetic drugs as modulators of stimulus-secretion coupling
Author: Atcheson, Robert
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 1994
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available