The diacylglycerols dioctanoylglycerol and oleoylacetylglycerol enhance prostaglandin synthesis by inhibition of the lysophosphatide acyltransferase.
Prostanoids are synthesized by resident macrophages upon stimulation with diacylglycerols. Oleoylacetylglycerol and dioctanoylglycerol induced prostaglandin E and thromboxane synthesis in a time- and concentration-dependent manner. Both diacylglycerols inhibited the lysophosphatide acyltransferase, which is the key enzyme in the reacylation of arachidonic acid. By this mechanism the pool of free arachidonic acid available for prostanoid synthesis is increased. Both diacylglycerols were able to inhibit the membrane-bound lysophosphatide acyltransferase by a direct interaction independent of protein kinase C. Thus lysophosphatide acyltransferase could be shown to be a new target of these diacylglycerols, known as activators of protein kinase C.
Goppelt-Strübe
M
M
Department of Pharmacology and Toxicology, Medical School Hannover, Federal Republic of Germany.
Pfannkuche
H J
HJ
Gemsa
D
D
Resch
K
K
D000217:Acyltransferases / Q000037:antagonists & inhibitors; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D011458:Prostaglandins E / Q000096:biosynthesis*
D004075:Diglycerides; D005989:Glycerides; D011458:Prostaglandins E; C044295:1,2-dioctanoylglycerol; C038237:1-oleoyl-2-acetylglycerol; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase