Phosphatidic acid and lysophosphatidic acid stimulate receptor-regulated membrane currents in the Xenopus laevis oocyte.
External application of dioleoyl-phosphatidic acid and oleoyl-lysophosphatidic acid stimulated Ca(2+)-dependent chloride currents in voltage-clamped Xenopus laevis oocytes. The responses were observed in oocytes from which follicular cells had been removed, indicating they were intrinsic to the oocyte itself. The lipid-induced Ca(2+)-dependent chloride currents were observed in the absence of extracellular calcium, were blocked by intracellular injection of the calcium chelator, bis(O-aminophenoxy)-ethane N,N,N'N'-tetraacetic acid, and could not be elicited by direct intracellular injection of the active lipids. The thresholds for dose-dependent current responses to dioleoyl-phosphatidic acid (100 nM) and for oleoyl-lysophosphatidic acid (10 nM) indicated that the lipid activities on oocytes were potent. With repeated or prolonged administration of either active lipid, responses exhibited desensitization. These results demonstrate that the Xenopus oocyte expresses endogenous functional responses for the mitogenic lipids phosphatidic acid and lysophosphatidic acid and thus provides a powerful model for characterization of the pharmacology and transduction pathways of these responses.
Ferguson
J E
JE
Department of Biological Chemistry, School of Medicine, University of California, Davis 95616-8635.
Hanley
M R
MR
D000818:Animals; D018118:Chloride Channels; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D007700:Kinetics; D008246:Lysophospholipids / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects / Q000502:physiology*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D010712:Phosphatidic Acids / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014982:Xenopus laevis
D018118:Chloride Channels; D007473:Ion Channels; D008246:Lysophospholipids; D008565:Membrane Proteins; D010712:Phosphatidic Acids; D011956:Receptors, Cell Surface; C037657:dioleoylphosphatidic acid; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D013755:Tetradecanoylphorbol Acetate; C032881:lysophosphatidic acid