Ethanol alters opioid regulation of Ca(2+) influx through L-type Ca(2+) channels in PC12 cells.
BACKGROUND
Studies at the behavioral and synaptic level show that effects of ethanol on the central nervous system can involve the opioid signaling system. These interactions may alter the function of a common downstream target. In this study, we examined Ca(2+) channel function as a potential downstream target of interactions between ethanol and μ or κ opioid receptor signaling.


METHODS
The studies were carried out in a model system, undifferentiated PC12 cells transfected with μ or κ opioid receptors. The PC12 cells express L-type Ca(2+) channels, which were activated by K(+) depolarization. Ca(2+) imaging was used to measure relative Ca(2+) flux during K(+) depolarization and the modulation of Ca(2+) flux by opioids and ethanol.


RESULTS
Ethanol, μ receptor activation, and κ receptor activation all reduced the amplitude of the Ca(2+) signal produced by K(+) depolarization. Pretreatment with ethanol or combined treatment with ethanol and μ or κ receptor agonists caused a reduction in the amplitude of the Ca(2+) signal that was comparable to or smaller than that observed for the individual drugs alone, indicating an interaction by the drugs at a downstream target (or targets) that limited the modulation of Ca(2+) flux through L-type Ca(2+) channels.


CONCLUSIONS
These studies provide evidence for a cellular mechanism that could play an important role in ethanol regulation of synaptic transmission and behavior through interactions with the opioid signaling.
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037, USA.
Donna L
DL
Gruol
Thomas E
TE
Nelson
Christine
C
Hao
Sarah
S
Michael
Vladana
V
Vukojevic
Yu
Y
Ming
Lars
L
Terenius
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D004347:Drug Interactions / Q000502:physiology; D004399:Dynorphins / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D057054:Molecular Imaging / Q000379:methods; D016716:PC12 Cells; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D020746:Calcium Channels, L-Type; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D000431:Ethanol; D004399:Dynorphins; D011188:Potassium; D002118:Calcium