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 lipids lysophosphatidic acid (acyl LPA) (3.73 nmol/g tissue) and lysoplasmanic acid (alkyl LPA) (0.44 nmol/g tissue). The presence of alkyl LPA was confirmed by mild alkaline hydrolysis analysis and by gas chromatography/mass spectrometry analysis of the trimethylsilyl derivative. This is the first clear evidence of the occurrence of an alkyl LPA in nature. The predominant molecular 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-containing species (7.2%) was also detected in the acyl LPA fraction. We also confirmed that rat brain alkyl LPA consists of 16:0-, 18:0- and 18:1-containing species. Noticeably, either acyl or alkyl LPA is capable of stimulating neuroblastomaxglioma hybrid NG108-15 cells to elicit a Ca(2+) transient, the potencies being almost the same. Both acyl and alkyl LPAs also induce cell rounding upon addition to the cells. These results suggest that acyl and alkyl LPAs play important physiological roles as intercellular signaling molecules as well as the roles as metabolic intermediates in the nervous system.
Sugiura
T
T
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan.
Nakane
S
S
Kishimoto
S
S
Waku
K
K
Yoshioka
Y
Y
Tokumura
A
A
Hanahan
D J
DJ
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002118:Calcium / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D004987:Ethers / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis; D008401:Gas Chromatography-Mass Spectrometry; D006868:Hydrolysis; D008246:Lysophospholipids / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D004987:Ethers; D005227:Fatty Acids; D008246:Lysophospholipids; D010972:Platelet Activating Factor; D002118:Calcium