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Effects of ethanol on muscarinic acetylcholine receptors in nerve cells

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Author

  • Murielle Hellsten Caron

Summary, in English

This thesis focused on the mechanisms involved in the effects of long-term ethanol treatment on mAChRs and their coupled-signal transduction pathway in human neuroblastoma SH-SY5Y cells. All 5 subtypes of mAChRs were expressed in these cells. Acute ethanol exposure induced a minor and transient decrease in the number of cell surface mAChRs, which could not account for the previously described pronounced and long-lasting inhibition of receptor-stimulated IP3 formation. Both mAChR number and stimulated PLC activity were increased after long-term ethanol treatment. Up-regulation of mAChRs was paralleled by a subtype-specific increase in mRNA levels of M1, M2, M4 and M5 mAChR subtypes, and a decrease in mRNA levels of the M3 mAChR subtype. Levels of M2 and M4 mRNA were most sensitive to the effects of ethanol. Together with the finding that up-regulated mAChRs after short ethanol exposure times were not capable of stimulating PLC, it is conceivable that these receptors may be M2 and/or M4 subtypes, with appearance of PLC-coupled mAChRs at the cell surface, first after prolonged ethanol exposure times. Our results also show that the ethanol-induced up-regulation of mAChR number can be blocked by both PKC and an NO-donor, and reproduced by PKC- and nNOS-inhibition. Furthermore, long-term ethanol treatment of the cells resulted in decreased levels of NO. Thus, PKC- and/or NO-dependent mechanisms may be involved in the long-term ethanol-induced up-regulation of mAChRs. On the other hand, the mechanisms involved in the ethanol-induced potentiation of mAChR-stimulated PLC activity were not PKC-sensitive, suggesting that at least 2 kinds of mechanisms are responsible for the effects of ethanol on mAChR number and PLC activity, a PKC-sensitive and a PKC-insensitive, respectively.

Publishing year

2002

Language

English

Document type

Dissertation

Publisher

Murielle Hellsten Caron, Medical Neurochemistry, Lund University Hospital, 221 85 Lund,

Topic

  • Neurology

Keywords

  • Klinisk kemi
  • Clinical chemistry
  • nerve cell
  • SH-SY5Y
  • NOS
  • PKC
  • PLC
  • Ethanol
  • mAChR

Status

Published

Supervisor

  • [unknown] [unknown]

ISBN/ISSN/Other

  • ISBN: 91-628-5085-7

Defence date

25 January 2002

Defence time

10:15

Defence place

Segerfalksalen, Wallenberg neurocentrum

Opponent

  • Ewa Hellström-Lindahl (Docent)