Propofol-induced Inhibition of Catecholamine Release Is Reversed by Maintaining Calcium Influx. (April 2016) - Han, Liping
Abstract : Background: Propofol (2, 6-diisopropylphenol) is one of the most frequently used anesthetic agents. One of the main side effects of propofol is to reduce blood pressure, which is thought to occur by inhibiting the release of catecholamines from sympathetic neurons. Here, the authors hypothesized that propofol-induced hypotension is not simply the result of suppression of the release mechanisms for catecholamines. Methods: The authors simultaneously compared the effects of propofol on the release of norepinephrine triggered by high K + -induced depolarization, as well as ionomycin, by using neuroendocrine PC12 cells and synaptosomes. Ionomycin, a Ca 2+ ionophore, directly induces Ca 2+ influx, thus bypassing the effect of ion channel modulation by propofol. Results: Propofol decreased depolarization (high K + )-triggered norepinephrine release, whereas it increased ionomycin-triggered release from both PC12 cells and synaptosomes. The propofol (30 μM)-induced increase in norepinephrine release triggered by ionomycin was dependent on both the presence and the concentration of extracellular Ca 2+ (0.3 to 10 mM; n = 6). The enhancement of norepinephrine release by propofol was observed in all tested concentrations of ionomycin (0.1 to 5 μM; n = 6). Conclusions: Propofol at clinically relevant concentrations promotes the catecholamine release as long as Ca 2+ influx is supported. This unexpected finding will allow for a better understanding in preventing propofol-induced hypotension. Abstract : Clinically relevant concentrations of propofol (10 to 30 μM) indeed inhibited the depolarization (by K + )-dependent norepinephrine release in cultured PC12 cells (which are derived from rat adrenal chromaffin cells) and synaptosomes. Unexpectedly, the same propofol concentrations that inhibited depolarization-dependent norepinephrine release increased ionomycin (a Ca 2+ ionophore)-triggered catecholamine release in a Ca 2+ -dependent manner. The Ca 2+ -dependent propofol-induced increase in ionomycin-triggered catecholamine release was abolished in the presence of the Ca 2+ chelator, EGTA.