Barbiturates inhibit K(+)-evoked noradrenaline and dopamine release from rat striatal slices--involvement of voltage sensitive Ca(2+) channels.
The cellular target site(s) for anaesthetic action remain unclear. In rat striatal slices we have previously demonstrated that K(+)-evoked noradrenaline (NA) and dopamine (DA) release is mediated predominantly via P/Q-type voltage sensitive Ca(2+) channels (VSCC). Using this model of Ca(2+) dependent transmitter release we have evaluated the effects of anaesthetic and non-anaesthetic barbiturates. Rat brain striatal slices were incubated in the absence and presence of barbiturate for 10 min at 37 degrees C. The slices were then incubated for 6 min with 40 mM KCl. All anaesthetic barbiturates produced a concentration-dependent inhibition of K(+)-evoked NA and DA release. Non-anaesthetic barbiturate, barbituric acid was ineffective. The pIC(50) for NA and DA release (thiopental: 4.90+/-0.13 and 5.00+/-0.10, pentobarbital: 4.39+/-0.07 and 4.43+/-0.14, phenobarbital: 3.85+/-0.08 and 3.59+/-0.10, respectively) correlated with lipid solubility (NA: r(2)=0.999, DA: r(2)=0.987). We therefore suggest that barbiturates inhibit catecholamine release via an interaction with P/Q VSCC further implicating this channel in anaesthetic action.
Hirota
K
K
Department of Anesthesiology, University of Hirosaki School of Medicine, 036-8563, Hirosaki, Japan.
Kudo
M
M
Kudo
T
T
Kitayama
M
M
Kushikata
T
T
Lambert
D G
DG
Matsuki
A
A
D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
D000777:Anesthetics; D001463:Barbiturates; D020864:Calcium Channels, N-Type; D004298:Dopamine; D009638:Norepinephrine; D011188:Potassium