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ANESTHETIC PHARMACOLOGY

Inhibition by Propofol of Intracellular Calcium Mobilization in Cultured Mouse Pituitary Cells

Anesthesiology Division, Hospital of Special Surgery, Weill Medical College of Cornell University, New York

Address correspondence to Jacques T. Ya Deau, Hospital for Special Surgery, Anesthesiology Division, Weill Medical College of Cornell University, 535 E 70 St., New York, NY 10021. Address e-mail to yadeauj{at}hss.edu

Propofol inhibited regulated secretion of the neuropeptide ß-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 µM) did not inhibit Ca²⁺-induced secretion of ß-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 µM; P < 0.05). Nitrendipine also inhibited potassium-induced Ca²⁺ peaks. Propofol 50 µM 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⁺.

IMPLICATIONS: 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.

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