Algal products as naturally occurring substrates for p-glycoprotein in Mytilus californianus

Mytilus californianus is a filter feeder that removes seaweed particulates, phytoplankton, and their byproducts from the water. The gills of this animal express high multixenobiotic resistance (MXR) and multixenobiotic transport activity that is related to the mammalian p-glycoprotein (p-gp). The high p-gp observed in mussel gills may provide the mussel protection from natural toxins in the diet. To test this hypothesis, extracts of various seaweeds and phytoplankton found in and around the mussel habitat were examined for presence of p-gp substrates by competition assays with a fluorescent dye substrate, rhodamine B. Accumulation of rhodamine was increased whereas dye efflux was slowed in the presence of algal extracts, indicating that p-gp substrates are present in the seaweeds Macrocystis pyrifera, Egregia menziesii, and Phyllospadix scouleri and the phytoplankton Alexandrium catanella and Pseudonitzchia australis. Initial fractionation of E. menziesii extracts by HPLC showed several distinct peaks of moderate hydrophobicity with p-gp-modulating ability. Additionally, Egregia extract showed potential as a chemosensitizer in tests with mussel (Mytilus edulis) and sea urchin (Lytechinus pictus) embryos. These data indicate that marine algae contain compounds that are substrates and/or chemosensitizers for the p-gp transporter in marine bivalves, thus providing evidence that MXR may have evolved in response to dietary pressures.