Regulation of the Endocannabinoid System in Endotoxicosis of Conscious Guinea Pigs

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Intestinal movements in conscious, unrestrained guinea pigs were observed by telemetry through a force transducer sutured to the taenia caecum. Following administration of lipopolysaccharide (LPS) and cannabinoids, the muscle tension of the taenia caecum decreased dose-dependently. Body temperature decreased in parallel with decreases in tension. Decreases in both these variables were suppressed by pre-treatment with AM281, a cannabinoid CB1 receptor antagonist, but not with AM630, a CB2 receptor antagonist. Following LPS administration, endocannabinoid levels in guinea pig plasma were measured using LC/MS/MS analysis. One hour following LPS administration, 2-arachidonoylglycerol (2-AG) levels had increased significantly, while arachidonoylethanolamide (AEA) levels were below detection limits. For mice, post-LPS survival rates in the presence of AM281 increased. The fact that LPS-induced decrease in muscle tension in taenia caecum is suppressed and post-LPS survival rates improved following administration of a CB1 receptor antagonist, suggests that a signaling pathway associated with the CB1 receptor plays a role in the pharmacological effects of LPS. Increases in blood 2-AG levels one hour after LPS administration suggest regulation of physiological responses by the endocannabinoid system during endotoxicosis.
一般社団法人日本救急医学会の論文