Avaliação do efeito do propofol na liberação deacetilcolina em sinaptosomas de hipocampo de ratos

Abstract

General anesthetics are widely used to induce general anesthesia but their molecular mechanisms of action remain undetermined. Propofol is an intravenous anesthetic commonly used for induction and maintenance of anesthesia and for sedation in the intensive care. This agent is capable of modifying synaptic transmission by altering the release of neurotransmitters in the presynaptic region and also modulating the response in the postsynaptic region. Among the effects caused by this agent the most commons are immobility, unconsciousness andamnesia. Acetylcholine (ACh) is a common distributed excitatory neurotransmitter in mammals brain that is involved in the regulation of consciousness, awakening, cognitive functions, memory and sleep disorders. The hippocampus is a brain region involved in memoryformation, learning and emotions. In the present study we investigated the effect of propofol on ACh release induced by veratridine, a voltage-dependent Na+ channel opening agent, and induced by KCl, a depolarizing agent capable of inducing calcium influx, in rat hippocampus synaptosomes and try to unravel the mechanisms of presynaptic action of this agent. The synaptosomes were incubated with [methyl-3H] choline chloride and subsequently confined in a perfusion chamber. The radioactive samples released were counted in a liquid scintillator. Propofol reduced spontaneous and evoked release of [3H] ACh and this result suggests that propofol effects on cholinergic transmission may be the reason that explains the physiological effect of amnesia characteristic of this agent. Upon stimulation with veratridine was possible to demonstrated that the mechanism of action of propofol involves the participation of voltage sensitive sodium channels, but wasnt possible torule out the involvement of extracellular and intracellular Ca2 + in this process. Upon stimulation with KCl was possible to demonstrate that the mechanism of action of propofol is independent of extracellular Ca2+ and depends on intracellular Ca2 +.