Occurrence of lysophosphatidic acid and its alkyl ether-linked analog in rat brain and comparison of their biological activities toward cultured neural cells

Rat brain was found to contain substantial amounts of potent bioactive lipi ds lysophosphatidic acid (acyl LPA) (3.73 nmol/g tissue) and lysoplasmanic acid (alkyl LPA) (0.44 nmol/g tissue). The presence of alkyl LPB was confir med by mild alkaline hydrolysis analysis and by gas chromatography/mass spe ctrometry analysis of the trimethylsilyl derivative. This is the first clea r evidence of the occurrence of an alkyl LPA in nature. The predominant mol ecular species of acyl LPA are 18:1-, 18:0- and 16:0-containing species (46 .9, 22.5 and 18.8%, respectively). A significant amount of a 20:4-containin g species (7.2%) was also detected in the acyl LPA fraction. We also confir med that rat brain alkyl LPA consists of 16:0-, 18:0- and 18:1-containing s pecies. Noticeably, either acyl or alkyl LPA is capable of stimulating neur oblastoma X glioma hybrid NG108-15 cells to elicit a Ca2+ transient, the po tencies being almost the same. Both acyl and alkyl LPAs also induce cell ro unding upon addition to the cells. These results suggest that acyl and alky l LPAs play important physiological roles as intercellular signaling molecu les as well as the roles as metabolic intermediates in the nervous system. (C) 1999 Elsevier Science B.V. All rights reserved.