PLEIOTROPIC UP-REGULATION OF NA-DEPENDENT COTRANSPORTERS BY RETINOIC ACID IN OPOSSUM KIDNEY-CELLS()

All-trans-retinoic acid (atRA) is a regulator of cellular growth and d ifferentiation. We investigated whether atRA can upregulate Nac-depend ent cotransporters in opossum kidney (OK) cells and thus increase upta ke from tubular fluid of several solutes needed for growth during earl y stages of ontogenesis. In OK cells, incubation with atRA for 24 h in creased the Na+ gradient-dependent cotransports of phosphate, L-prolin e, L-glutamic acid, and SO42- by a similar degree (similar to 40%) tha t was prevented by pretreatment with actinomycin D. In contrast, activ ities of other Na+-dependent transporters, Na+-K+-adenosinetriphosphat ase, gamma-glutamyltranspeptidase, and leucine aminopeptidase, were un changed by atRA. Cell proliferation determined by [H-3]thymidine incor poration was not increased by atRA. The stimulatory effects of atRA an d 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 analogo us time course and to a similar extent as observed in OK cells. We con clude that atRA stimulates several Na+-dependent cotransporters via a genomic mechanism and may represent a synchronous adaptation to nutrit ional requirements of early phases of ontogenesis.