EFFECTS OF PROPOFOL AND THIOPENTONE ON POTASSIUM-EVOKED AND CARBACHOL-EVOKED [H-3] NORADRENALINE RELEASE AND INCREASED [CA2-SY5Y HUMAN NEUROBLASTOMA-CELLS(](I) FROM SH)

We have examined the effects of two intravenous anaesthetic induction agents, propofol and thiopentone, on K+ and carbachol evoked [H-3]nora drenaline release from a human neuroblastoma cell line, SH-SY5Y. In th is model, we have previously demonstrated that K+ evoked [H-3]noradren aline release was dependent on Ca2+ entry and carbachol evoked release was extracellular Ca2+-independent. Propofol inhibited K+ (100 mM)-ev oked (IC50 of 42 +/- 11 mu M), but not carbachol (1 mM)-evoked, [H-3]n oradrenaline release. Thiopentone inhibited both K+- and carbachol-evo ked release with IC50 values of 116 +/- 15 mu M and 169 +/- 39 mu M, r espectively. These inhibitory effects were not due to changes in the r elease dynamics, as assessed using perfused cells. Furthermore, thiope ntone inhibition of carbachol-evol,ed release was not due to muscarini c receptor antagonism Both propofol and thiopentone caused noncompetit ive inhibition of K+-stimulated Ca2+ influx, with IC50 values of 127 /- 7 mu M and 121 +/- 10 mu M, respectively. These effects were not du e to interaction with GABA(A) receptors, but suggest that both compoun ds block voltage-sensitive Ca2+ channels. Thiopentone, but not propofo l, inhibited carbachol-stimulated increased intracellular Ca2+ concent rations in the presence and absence of extracellular Ca2+ However, thi opentone had no effect on carbachol-stimulated inositol (1,4,5)-tripho sphate formation, suggesting that thiopentone may directly inhibit Ca2 + release from intracellular stores.