Bovine serum albumin and lysophosphatidic acid stimulate calcium mobilization and reversal of cAMP-induced stellation in rat spinal cord astrocytes.

We report that lysophosphatidic acid (LPA) stimulates dynamic calcium (Ca2+) fluctuations and morphological rearrangements in astrocytes derived from neonatal rat spinal cord. Addition of 10 microM LPA elicited single Ca2+ transients, or biphasic oscillations and sustained increases in intracellular Ca2+ ([Ca2+]i). The biphasic Ca2+ response consisted of an initial release from intracellular stores, often followed by a sustained elevation or continued oscillations that required Ca2+ flux across the cell membrane. The type of Ca2+ response, but not the overall magnitude, was dependent on LPA concentration. Higher concentrations (> 10 microM) often elicited sustained increases in [Ca2+]i, while lower concentrations stimulated oscillations or single Ca2+ transients. It has previously been established that agents that elevate cyclic adenosine monophosphate (cAMP) induce flat astrocytes to adopt a more stellate morphology. LPA can completely reverse this morphological change at a half-maximal concentration of 215 nM. Inhibiting LPA-induced [Ca2+]i fluctuations using BAPTA-AM to buffer [Ca2+]i and EGTA in the bath to prevent transmembrane flux had little effect on the ability of LPA to reverse stellation. LPA is found bound to serum albumin, in which crude preparations have been shown to induce various physiological responses in a number of cell types. Many of the activities have been attributed to albumin-associated lipid factors including LPA. We show that lipid factors associated with BSA can mimic the effect of LPA in both Ca2+ mobilization and reversal of cAMP-induced stellation.