Inhibition by propofol of intracellular calcium mobilization in cultured mouse pituitary cells.
Propofol inhibited regulated secretion of the neuropeptide beta-endorphin from AtT-20 cells, a pituitary tumor cell line. Neuropeptide secretion depends on an increase of intracellular calcium (Ca(2+)) levels. We investigated the hypothesis that propofol altered intracellular Ca(2+) levels in AtT-20 cells. Propofol (100 microM) did not inhibit Ca(2+)-induced secretion of beta-endorphin from digitonin-permeabilized cells. Thus, propofol did not inhibit neuropeptide secretion by blocking the effects of increased intracellular Ca(2+). Intracellular Ca(2+) was measured in intact cells using a Ca(2+)-sensitive dye. Ca(2+) transients were generated by depolarization with KCl or by incubation with thapsigargin (an inhibitor of Ca(2+) uptake into the endoplasmic reticulum). Propofol inhibited generation of Ca(2+) transients in intact cells by KCl (half-maximal inhibitory concentration of 14.9 microM; P < 0.05). Nitrendipine also inhibited potassium-induced Ca(2+) peaks. Propofol 50 microM reduced the thapsigargin-induced Ca(2+) peak to 47% of control (P < 0.05). Thapsigargin-induced Ca(2+) peaks were not affected by calcium channel blockade by nitrendipine. Propofol inhibited the stimulus-induced increase in intracellular Ca(2+). Propofol inhibited thapsigargin-induced Ca(2+) transients, but nitrendipine did not, indicating that propofol had effects on intracellular Ca(2+) independent of blockade of L-type Ca(2+) channels. Propofol may inhibit release of Ca(2+) from intracellular stores. These results are consistent with the hypothesis that propofol inhibits neuropeptide secretion by inhibiting the stimulus-induced increase in intracellular Ca(2+).


CONCLUSIONS
Propofol may block both entry of calcium into cells and release of calcium from intracellular stores, thereby inhibiting regulated secretion of neuropeptides. Study of the effects of propofol on intracellular calcium metabolism may increase understanding of how propofol alters brain function and may aid development of better IV anesthetics.
Anesthesiology Division, Hospital of Special Surgery, Weill Medical College of Cornell University, New York.
Jacques T
JT
Ya Deau
Christine M
CM
Morelli
Soléenne
S
Desravines
D018686:Anesthetics, Intravenous; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D051379:Mice; D009479:Neuropeptides / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D001615:beta-Endorphin / Q000378:metabolism
D018686:Anesthetics, Intravenous; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D009479:Neuropeptides; D001615:beta-Endorphin; D011189:Potassium Chloride; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium; D016257:Fura-2; D015742:Propofol