Dioleoyl phosphatidic acid induces morphological changes through an endogenous LPA receptor in C6 glioma cells.
Previously, we suggested that dioleoyl phosphatidic acid (PA) and lysophosphatidic acid (LPA) increased [Ca(2+)](i) through endogenous LPA receptors coupled to pertussis toxin-sensitive G proteins in rat C6 glioma cells. In the present report, we investigated morphological changes and cytotoxicity induced by PA and LPA in C6 glioma cells. Isoproterenol treatment led to changes in the cell morphology of rat C6 glioma cells, which were reverted by the addition of PA and LPA. PA-and LPA-induced morphological reversions were inhibited by treatment with Ki16425, an LPA(1)/LPA(3) receptor antagonist. VPC32183, another LPA(1)/LPA(3) receptor antagonist with a different structure, only inhibited PA-induced morphological reversion but not LPA-induced reversion. However, the reversions were not inhibited by treatment with pertussis toxin, a specific inhibitor of G(i/o) proteins. In addition, cytotoxicity was only induced by LPA but not by PA in C6 glioma cells. Our results suggest that PA may act as a partial agonist at endogenous LPA receptors, which are sensitive to Ki16425 and coupled to PTX-insensitive G proteins, to evoke morphological changes in C6 glioma cells.
Chang
Young-Ja
YJ
Laboratory of Pharmacology, Pusan National University, Busan, Republic of Korea.
Kim
Yu-Lee
YL
Jo
Ji-Yeong
JY
Kyeok
Kim
K
Kim
Hyo-Lim
HL
Im
Dong-Soon
DS
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000494:pharmacology*; D054333:Drug Partial Agonism; D005910:Glioma; D007545:Isoproterenol / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology* / Q000502:physiology; D010755:Organophosphates / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000494:pharmacology* / Q000502:physiology; D011422:Propionates / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D049368:Receptors, Lysophosphatidic Acid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
C477898:3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid; D003603:Cytotoxins; D007555:Isoxazoles; D008246:Lysophospholipids; D010755:Organophosphates; D010712:Phosphatidic Acids; D011422:Propionates; D011725:Pyridines; D049368:Receptors, Lysophosphatidic Acid; C529824:VPC32183; C037657:dioleoylphosphatidic acid; D037342:Pertussis Toxin; D007545:Isoproterenol; C032881:lysophosphatidic acid