Prostaglandins and leukotrienes

Prostaglandins are molecules that behave like hormones and are used for signaling between cells. They are produced by many cell types and tissues in the body.

To make prostaglandins, an enzyme called phospholipase A2 turns diacylglycerol into arachidonic acid (AA). All prostaglandins are derived from AA and this molecule is mentioned often in scientific literature about mast cells, as it is easier to detect AA than some prostaglandins. Once AA has been produced, one of two things happen: AA is either changed by the cyclooxygenase (COX) pathway into prostaglandins and thromboxanes or by the lipoxygenase (LO) pathway into leukotrienes.

Prostaglandins, thromboxanes and leukotrienes are all types of eicosanoids. Eicosanoid is another common word in mast cell literature, and in that context it usually refers to prostaglandins or leukotrienes.

To make prostaglandins from AA, cells use the enzymes COX-1 and COX-2. COX-1 produces regular low levels of prostaglandins, whereas COX-2 makes prostaglandins in response to inflammation. Other enzymes called prostaglandin synthases finish off making the prostaglandins into the right shapes. To make leukotrienes from AA, cells use the enzyme arachidonate 5-lipoxygenase.

There are a number of medications that interfere with the production of leukotrienes or prostaglandins by interfering with the enzymes that make them. This is generally regarded as a more effective way to treat symptoms from these products, rather than trying to block their action after they have been made.

Non steroidal anti-inflammatories (NSAIDs), of which there are dozens, interfere with the activity of both COX-1 and COX-2. Newer COX-2 inhibitors like Celebrex only inhibit COX-2. Vitamin D downregulates expression of COX-2. A chemical in St. John’s Wort is also a COX-1 inhibitor. Zileuton is a lipoxygenase inhibitor.