2-Arachidonoyl-sn-glycero-3-phosphate, an arachidonic acid-containing lysophosphatidic acid: occurrence and rapid enzymatic conversion to 2-arachidonoyl-sn-glycerol, a cannabinoid receptor ligand, in rat brain.
A substantial amount of lysophosphatidic acid (LPA) (15.66 nmol/g tissue) was found to occur in the brain isolated from rats killed in liquid nitrogen. We found that a significant portion of brain LPA was accounted for by the arachidonic acid-containing species (5.4%). We obtained evidence that both 2-arachidonoyl species and 1-arachidonoyl species of LPA are present. The occurrence of 2-arachidonoyl LPA in the brain (0.53 nmol/g tissue) is a notable observation, because of its structural resemblance to 2-arachidonoyl-sn-glycerol (2-AG), an endogenous cannabinoid receptor ligand. We then examined the biological activity of 2-arachidonoyl LPA and compared it with that of 2-AG using neuroblastoma x glioma hybrid NG108-15 cells which express both the LPA receptor and cannabinoid CB1 receptor. We found that 2-arachidonoyl LPA interacts with the LPA receptor(s) to elicit the elevation of intracellular free Ca(2+) concentrations, whereas 2-AG interacts exclusively with the cannabinoid CB1 receptor. Next, we examined the possible metabolic relationship between 2-arachidonoyl LPA and 2-AG and obtained clear evidence that rapid enzymatic conversion of 2-arachidonoyl LPA to 2-AG took place in the brain homogenate. It is noteworthy that two types of endogenous ligands, that interact with different types of receptors, are closely related metabolically and rapidly interconvert.
Nakane
Shinji
S
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Tsukui-gun, Kanagawa 199-0195, Japan.
Oka
Saori
S
Arai
Shunsuke
S
Waku
Keizo
K
Ishima
Yoshio
Y
Tokumura
Akira
A
Sugiura
Takayuki
T
D000818:Animals; D001095:Arachidonic Acids; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D005989:Glycerides / Q000378:metabolism*; D008024:Ligands; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism*
C459464:2-arachidonoyl-sn-glycero-3-phosphate; D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D008024:Ligands; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C094503:glyceryl 2-arachidonate; D002118:Calcium