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.

Direct hemoperfusion through a network of immobilized polymyxin B fibers is used for the treatment of septic shock, but the mechanism underlying the clinical benefits remains unclear. The aims of the present study were to assess the actions of direct hemoperfusion through immobilized polymyxin B fibers on effects of exogenous endotoxin or 2-arachidonoylglycerol in conscious guinea pigs; and to examine the underlying mechanisms. In the present study, colonic motion was monitored continuously by telemetry using a force transducer attached to the taenia caecum, while blood pressure was monitored with a carotid artery catheter. To establish a hemoperfusion circuit in a freely moving, conscious guinea pig, catheters were implanted in the carotid artery and the jugular vein, tunneled subcutaneously, exteriorized at the back of the neck in contact with a lightweight tethering spring, and attached to a swivel device at the top of the cage. On the day after the operation, lipopolysaccharide (Escherichia coli, O111:B4; 1 mg/kg) or 2-arachidonoylglycerol (1 mg/kg) was given intraperitoneally (i.p.) and direct hemoperfusion through immobilized polymyxin B fibers was carried out for 2 h. The results showed that in guinea pigs treated with direct hemoperfusion through immobilized polymyxin B fibers, relaxation of colonic longitudinal muscle caused by lipopolysaccharide or 2-arachidonoylglycerol was significantly suppressed, as were decreases in blood pressure. We conclude that the actions following exogenous administration of 2-arachidonoylglycerol were eliminated by direct hemoperfusion through immobilized polymyxin B fibers. These results suggest that effectiveness of direct hemoperfusion through immobilized polymyxin B fibers in endotoxemia involves elimination of 2-arachidonoylglycerol action.

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