Inhibition by propofol of intracellular calcium mobilization in cultured mouse pituitary cells

Propofol inhibited regulated secretion of the neuropeptide P-endorphin from AtT-20 cells, a pituitary tumor cell line. Neuropeptide secretion depends on an increase of intracellular calcium (Ca2+) levels. We investigated the hypothesis that propofol altered intracellular Ca2+ levels in AtT-20 cells. Propofol (100 muM) did not inhibit Ca2+- induced secretion of P-endorphin from digitonin-permeabilized cells. Thus, propofol did not inhibit neuropeptide secretion by blocking the effects of increased intracellular Ca2+. Intracellular Ca2+ was measured in intact cells using a Ca2+-sensitive dye. Ca2+ transients were generated by depolarization with KCl or by incubation with thapsigargin (an inhibitor of Ca2+ uptake into the endoplasmic reticulum). Propofol inhibited generation of Ca2+ transients in intact cells by KCl (half-maximal inhibitory concentration of 14.9 muM; P < 0.05). Nitrendipine also inhibited potassium-induced Ca2+ peaks. Propofol 50 muM reduced the thapsigargin-induced Ca2+ peak to 47% of control (P < 0.05). Thapsigargin-induced Ca2+ peaks were not affected by calcium channel blockade by nitrendipine. Propofol inhibited the stimulus- induced increase in intracellular Ca2+. Propofol inhibited thapsigargin-induced Ca2+ transients, but nitrendipine did not, indicating that propofol had effects on intracellular Ca2+ independent of blockade of L-type Ca2+ channels. Propofol may inhibit release of Ca2+ from intracellular stores. These results are consistent with the hypothesis that propofol inhibits neuropeptide secretion by inhibiting the stimulus-induced increase in intracellular Ca2+.