Xenopus oocytes express multiple receptors for LPA-like lipid mediators

In Xenopus laevis oocytes, both lysophosphatidic acid (LPA) and a cyclic phosphate-containing analogue 1-acyl-sn-glycero-2,3-cyclic phosphate (cLPA) isolated from Physarum polycephalum activate oscillatory Cl- currents. cLPA elicited oscillatory currents only when applied extracellularly and, similarly to LPA, evoked homologous desensitization. cLPA applied to oocytes previously desensitized by LPA failed to elicit a current, indicating that LPA completely desensitized the cLPA receptors. In contrast, when oocytes were desensitized by cLPA, LPA still evoked large currents. The lack of heterologous desensitization between cLPA and LPA indicates that the former acts on a distinct receptor subpopulation(s), which is also activated by LPA. The alkyl-ether analogue 1-hexadecyl-2-lyso-sn-glycero-3-phosphate (16:0-GP) and dioleoyl-phosphatidic acid (18:1-PA) showed heterologous desensitization patterns similar to that of LPA with regard to cLPA. Complete heterologous desensitization was obtained between LPA and 16:0-GP or 18:1-PA. These observations demonstrate the simultaneous expression of at least two different types of receptors for LPA-like lipid mediators on Xenopus oocytes and that these receptors show different pharmacological properties in their selectivity to cLPA.