Phospholipase A activity in the skin. Modulators of arachidonic acid release from phosphatidylcholine

Abstract

The distribution of the hydrolysis of 1-acyl-2-[1-14C]arachidonoyl-sn-glycero-3-phosphocholine and the simultaneous biosynthesis of prostaglandins by subcellular fractions from human and rat skin membrane preparations were determined. The phospholipase A2 activity was distributed among the subcellular particulate preparations with the highest specific activity in the 105000g particulate fraction. The activity was optimal at pH 7.5 in the presence of 1.0 mM-CaCl2 and was inhibited by EDTA. The hydrolysis of phosphatidylcholine by the skin 105000g particulate fraction was inhibited by cortisol and triamcinolone acetonide and it was stimulated by histamine, bradykinin, retinoic acid and cholera enterotoxin (freeze-dried Vibrio cholerae). Furthermore hydrolysis of phosphatidylcholine by the skin phospholipase A was also enhanced by low concentrations of prostaglandin E2 and prostaglandin F2 alpha. These last results suggest that the amplication of the hydrolysis of phosphatidylcholine by prostaglandin E2 and prostaglandin F2 alpha, with the consequent release of arachidonic acid (the substrate of prostaglandin synthesis) is likely a positive-feedback regulation of the arachidonic acid-prostaglandin cascade.

Ultraviolet Radiation Stimulates the Release of Arachidonic Acid From Mammalian Cells in Culture*

“…The inhibition with the corticosteroid was more marked than with the latter compound. Dexamethasone has been shown to inhibit phospholipase A2 activity in a number of systems but has a wide range of effects on cellular metabolism (Ziboh and Lord, 1979). The inhibition of phospholipase has been shown to depend on corticosteroid induced cellular production of a protein, lipomodulin (macrocortin) which binds to the phospholipase molecule inhibiting it's activation (Hirata, 1983).…”

“…In mammalian cells this unsaturated fatty acid most frequently is esterified to the second carbon of the glycerol backbone in membrane phospholipids. Hydrolysis and release of fatty acid from this position is most likely catalyzed by a calcium-dependent phospholipase A2 enzyme which has been shown to be present in human skin (Ziboh and Lord, 1979). A two step process involving activation of both a phospholipase C and a diacylglycerol lipase has also been postulated as a mechanism for release of unsaturated fatty acid (Bell et al, 1979).…”

Phospholipases Induce Melanogenesis in Organ‐Cultured Skin

“…Phospholipase (PL) A2 (EC3.1.1.4) is a rate-limiting enzyme responsible for liberation of arachidonic acid (AA) and lysophospholipids, which are subsequently metabolized to eicosanoids, such as PG and LT, and platelet-activating factor (PAF), respectively. The activity of PLAz in the skin or that in cultured keratinocytes are induced by exposure to UV radiation (13)(14)(15)(16)(17). Phospholipase C or PLD also leads to the generation of AA or DAG from the membrane phospholipids after some stimulation ( 18).…”

Sulphido‐leukotriene production from peripheral leukocytes and skin in clinically normal dogs and house dust mite positive atopic dogs

“…Also, glucocorticoids and antihistamines were discontinued 2 months and 2 weeks, respectively, prior to inclusion in the study because they can interfere with IDST and LT synthesis 3 , 7 . Specifically, glucocorticoids inhibit phospholipase A 2 (PLA 2 ) which is the enzyme responsible for arachidonic acid release and ultimately LT synthesis, while histamine stimulates this enzyme 27 …”