Effect of Propofol on the Release of [3H] Acetylcholine from Rat Hippocampal Synaptosomes

Several studies have demonstrated that propofol interferes with acetylcholine (ACh) release in the central nervous system but the mechanism (s) involved remains unclear. The present study aimed to evaluate the mechanism (s) by which this agent interferes with the release of this neurotransmitter from rat hippocampal synaptosomes. Synaptosomes labeled with [H-3]ACh were superfused using an apparatus set up to collect 2 min fractions. The synaptosomes were perfused in the absence or presence of propofol, tetrodotoxin (Na+ channel blocker), EGTA (chelator of extracellular Ca2+), dantrolene (inhibitor of Ca2+ release through ryanocline receptors), 2-APB (antagonist of IP3 receptors) or BAPTA-AM (chelator of intracellular Ca2+) prior to the evoked-release of [H-3]ACh by KCl (50 mM) which is a Na+-independent stimuli or veratridine (50 mu M) which is a Na+-dependent stimuli. Basal release of [H-3]ACh was significantly decreased in the presence of propofol (1-1000 mu M). The anesthetic also decreased the release of [H-3]ACh evoked by veratridine and KCl (p<0.05). Tetrodotoxin (1.0 nM) reduced the veratridine-evoked release of [H-3]ACh (p<0.05). The simultaneous perfusion of the synaptosomes with tetrodotoxin (1.0 nM) and propofol (100 mu M) did not enhance the effects of these agents on veratridine-induced release of [H-3]ACh. EGTA (0.2 mM) significantly reduced the KCl-evoked release of [[H-3]ACh and increased the inhibitory effect of propofol (25 mu M) on the KCl-induced release of [H-3]ACh (p<0.05). BAPTA-AM, dantrolene and 2-APB decreased the KCl-evoked release of the neurotransmitter (p<0.05) but simultaneous perfusion of the synaptosomes with propofol and BAPTA-AM, propofol and dantrolene or propofol and 2-APB did not enhance the effects of these agents on KCl-induced release of [H-3]ACh. In conclusion, it seems that propofol decreased the release of ACh in the rat hippocampus by interfering with Na+ channels and the release of Ca2+ from internal stores.