Pleiotropic upregulation of Na plus -dependent cotransporters by retinoic acid in opossum kidney cells

All-trans-retinoic acid (atRA) is a regulator of cellular growth and differentiation. We investigated whether atRA can upregulate Nac-dependent cotransporters in opossum kidney (OK) cells and thus increase uptake from tubular fluid of several solutes needed for growth during early stages of ontogenesis. In OK cells, incubation with atRA for 24 h increased the Na+ gradient-dependent cotransports of phosphate, L-proline, L-glutamic acid, and SO42- by a similar degree (similar to 40%) that was prevented by pretreatment with actinomycin D. In contrast, activities of other Na+-dependent transporters, Na+-K+-adenosinetriphosphatase, gamma-glutamyltranspeptidase, and leucine aminopeptidase, were unchanged by atRA. Cell proliferation determined by [H-3]thymidine incorporation was not increased by atRA. The stimulatory effects of atRA and phosphate deprivation on Na+-P-i cotransport demonstrated additivity, whereas the combination of atRA. and 3,5,3'-triiodothyronine did not. atRA stimulated Na+-P-i cotransport in LLC-PK1 cells with an analogous time course and to a similar extent as observed in OK cells. We conclude that atRA stimulates several Na+-dependent cotransporters via a genomic mechanism and may represent a synchronous adaptation to nutritional requirements of early phases of ontogenesis.