Genetic inactivation and prolonged pharmacologic inhibition of monoacylglycerol lipase have opposite effects on anesthetic sensitivity to propofol

摘要: Monoacylglycerol lipase (MGL) is a major enzyme involved in degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG). Selective inhibitors MGL are regarded as promising analgesics and anticancer agents. To gain insight into possible consequences their prolonged administration for anesthetic action, effects several inhalational intravenous anesthetics were tested knockout mice lacking gene loss righting reflex (LORR) assay. Sensitivity to most was not altered mice. However, compared with wild-type littermates, they showed increased sensitivity propofol. Permanently elevated levels 2-AG after known cause desensitization cannabinoid (CB1) receptors, which have been advocated mediators propofol anesthesia. Therefore, at first suggested that may potentiate CB1 receptors despite hypofunction these animals. Pharmacologic inhibition also causes so further C57BL/6N pretreated chronically selective inhibitor JZL 184. Contrary results mice, animals drastically reduced The reason remains unclear, but result from changes occurring during development. our 184 confirmed role anesthesia previously, suggest use be associated development resistance