Signaling of lysophosphatidic acid-evoked chloride current: calcium release from inositol trisphosphate-sensitive store.

In Xenopus oocytes, lysophosphatidic acid (LPA) evoked inward currents at the holding potential of -60 mV, which were quickly desensitized upon repeated challenges of the compound at 10 nM or 1 microM. This desensitization was prevented by pretreatment with protein kinase A inhibitor or recovered by its post-treatment, but not by the pretreatment with an inhibitor of protein kinase C or calmodulin kinase II. From pharmacological studies, the LPA-evoked currents were found to be mediated by phospholipase C, calcium-mobilization from thapsigargin-sensitive Ca2+ stores, araguspongine E-sensitive inositol trisphosphate receptor, and calcium-dependent chloride channels.