2‐Arachidonoyl glycerol suppresses gastric emptying via the cannabinoid receptor 1‐cholecystokinin signaling pathway in mice

Abstract

2‐Monoacylglycerol (2‐MAG) is one of the digestion products of dietary lipids. We recently demonstrated that a 2‐MAG, 2‐arachidonoyl glycerol (2‐AG) potently stimulated cholecystokinin (CCK) secretion via cannabinoid receptor 1 (CB1) in a murine CCK‐producing cell line, STC‐1. CCK plays a crucial role in suppressing postprandial gastric emptying. To examine the effect of 2‐AG on gastric emptying, we performed acetaminophen and phenol red recovery tests under oral or intraperitoneal administration of 2‐AG in mice. Orally administered 2‐AG (25 mg/kg) suppressed the gastric emptying rate in mice, as determined by the acetaminophen absorption test and phenol red recovery test. Intraperitoneal administration of a cholecystokinin A receptor antagonist (0.5 mg/kg) attenuated the gastric inhibitory emptying effect. In addition, both oral (10 mg/kg) and intraperitoneal (0.5 mg/kg) administration of a CB1 antagonist counteracted the 2‐AG‐induced gastric inhibitory effect. Furthermore, intraperitoneal 2‐AG (25 mg/kg) suppressed gastric emptying. These results indicate that 2‐AG exhibits an inhibitory effect on gastric emptying in mice, possibly mediated by stimulating both CCK secretion via CB1 expressed in CCK‐producing cells and acting on CB1 expressed in the peripheral nerves. Our findings provide novel insights into the 2‐MAG‐sensing mechanism in enteroendocrine cells and the physiological role of 2‐MAG.

Effects of laparoscopic and choledochoscopic gallbladder-preserving cholecystolithotomy on levels of operation indicators, gallbladder function, and cholecystokinin type-A receptor in patients with gallstones.

“…Furthermore, high-level CCKAR can increase the water in the colon and promote adequate absorption of bile salts after operation, thereby preventing bile salts from entering the intestines to induce stress responses [ 20 , 21 ]. Low-level CCKAR can lead to abnormal gallbladder function, which is unfavourable for the recovery of digestive function and even triggers gastrointestinal complications like biliary tract infection, peritonitis, and haemobilia [ 22 ]. LRH-1 can enhance the transformation of total cholesterol and promotes the transfer of total cholesterol from hepatocytes to bile, and the supersaturated precipitation of total cholesterol in bile can accelerate the formation of gallstones.…”

Protective effects of Liupao tea against high-fat diet/cold exposure-induced irritable bowel syndrome in rats

“…Then, the abdominal cavity of each rat was opened and the cardiac sphincter and distal pylorus were ligated to obtain the stomach. Gastrointestinal function-related indicators, including the gastric emptying rate, fecal water content, and intestinal water content, were measured and slightly modified per published articles [ 23 , 24 ].…”