Brainy Route To Prostaglandins

Prostaglandins are produced via a different pathway in the brain than elsewhere in the body, scientists report (Science, DOI: 10.1126/science.1209200). These inflammation mediators are made by cyclooxygenase (COX) enzymes using arachidonic acid as a precursor. Researchers have assumed that phospholipase A₂ enzymes are the primary source of that arachidonic acid, but Daniel K. Nomura of the University of California, Berkeley; Benjamin F. Cravatt of Scripps Research Institute; and coworkers show that in the brain the enzyme monoacylglycerol lipase (MAGL) hydrolyzes the endocannabinoid 2-arachidonoylglycerol to produce the arachidonic acid used to make prostaglandins. Mice treated with a MAGL inhibitor produced less arachidonic acid and prostaglandins in response to the proinflammatory agent lipopolysaccharide. MAGL could be a good target for anti-inflammatory medications without the gastrointestinal effects of drugs that target COX enzymes, the researchers suggest. Lawrence J. Marnett, a prostaglandin expert at Vanderbilt University, says, “This work will rewrite textbooks on the biochemistry of prostaglandin generation in the brain.”